Публикации о генах и старении (titles)

Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status.

Abstract

The impact of nutrition on the metabolic profile of osteoporosis (OS) is unknown. Identify biochemical factors driving the association of fruit and vegetable (FV) intakes with OS prevalence using an untargeted metabolomics approach. Cross-sectional dietary, anthropometric and plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, n = 600 (46-79 yr). Bone mineral density was assessed by DXA. OS was defined by clinical standards. A culturally adapted FFQ assessed usual dietary intake. Principal components analysis (PCA) of 42 FV items created 6 factors. Metabolomic profiles derived from plasma samples were assessed on a commercial platform. Differences in levels of 525 plasma metabolites between disease groups (OS vs no-OS) were compared using logistic regression; and associations with FV intakes by multivariable linear regression, adjusted for covariates. Metabolites significantly associated with OS status or with total FV intake were analyzed for enrichment in various biological pathways using Mbrole 2.0, MetaboAnalyst, and Reactome, using FDR correction of P-values. Correlation coefficients were calculated as Spearman's rho rank correlations, followed by hierarchical clustering of the resulting correlation coefficients using PCA FV factors and sex-specific sets of OS-associated metabolites. High FV intake was inversely related to OS prevalence (Odds Ratio = 0.73; 95% CI = 0.57, 0.94; P = 0.01). Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. Important processes identified with OS-associated metabolites were steroid hormone biosynthesis in women and branched-chain amino acid metabolism in men. Factors derived from PCA were correlated with the OS-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among middle-aged and older adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links.

MeSH Terms

-

Keywords

Aging; Metabolism; Metabolomics; Nutrition; Osteoporosis; Puerto Rican; Sex steroids

A case of comorbidities highlighting cerebral stroke, vision impairment, and dementia.

Abstract

This case report is of a two-time stroke survivor with significant health comorbidities. This report highlights A.R.'s pre-existing, non-neurological vision impairments, stroke-related vision impairments, in addition to cognitive impairment and possible dementia. Information including her past medical history, current functional status, and battery of assessments that were used in the acute care hospital are detailed. Conclusions include the need for comprehensive, valid, and adapted assessments especially when comorbidities are present. We suggest that cognitive assessments that do not rely on vision may have improved the test accuracy in this case.

MeSH Terms

-

Keywords

Visual impairment; aging; comorbidities; dementia; neuro-ophthalmology; stroke

Whole blood DNA methylation aging markers predict colorectal cancer survival: a prospective cohort study.

Abstract

Blood DNA methylation-based aging algorithms predict mortality in the general population. We investigated the prognostic value of five established DNA methylation aging algorithms for patients with colorectal cancer (CRC). AgeAccelHorvath, AgeAccelHannum, DNAmMRscore, AgeAccelPheno and AgeAccelGrim were constructed using whole blood epi-genomic data from 2206 CRC patients. After a median follow-up of 6.2 years, 1079 deaths were documented, including 596 from CRC. Associations of the aging algorithms with survival outcomes were evaluated using the Cox regression and survival curves. Harrell's C-statistics were computed to investigate predictive performance. Adjusted hazard ratios (95% confidence intervals) of all-cause mortality for patients in the third compared to the first tertile were 1.66 (1.32, 2.09) for the DNAmMRscore, 1.35 (1.14, 1.59) for AgeAccelPheno and 1.65 (1.37, 2.00) for AgeAccelGrim, even after adjustment for age, sex and stage. AgeAccelHorvath and AgeAccelHannum were not associated with all-cause or CRC-specific mortality. In stage-specific analyses, associations were much stronger for patients with early or intermediate stage cancers (stages I, II and III) than for patients with metastatic (stage IV) cancers. Associations were weaker and less often statistically significant for CRC-specific mortality. Adding DNAmMRscore, AgeAccelPheno or AgeAccelGrim to models including age, sex and tumor stage improved predictive performance moderately. DNAmMRscore, AgeAccelPheno and AgeAccelGrim could serve as non-invasive CRC prognostic biomarkers independent of other commonly used markers. Further research should aim for tailoring and refining such algorithms for CRC patients and to explore their value for enhanced prediction of treatment success and treatment decisions.

MeSH Terms

-

Keywords

Aging; Colorectal cancer; DNA methylation; Mortality; Prognosis; Whole blood

Coordination in the unfolded protein response during aging in outbred deer mice.

Abstract

Endoplasmic reticulum (ER) stress has been linked to various metabolic pathologies, neurodegeneration and aging. Although various mechanistic aspects of the resulting unfolded protein response (UPR) have been elucidated, its regulation in genetically diverse populations remains elusive. In the present study we evaluated the expression of chaperones BiP/GRP78, GRP94 and calnexin (CANX) in the lungs, liver and brain of 7 months old and 2-3 years old outbred deer mice P. maniculatus and P. leucopus. Chaperones' expression was highly variable between species, tissues and ages suggesting that levels of expression of individual chaperones do not change consistently during aging. Despite this variation, a high degree of coordination was maintained between chaperones' expression indicating the tight regulation of the UPR which is consistent with its adaptive activity to maintain homeostasis. In the brain though of older P. maniculatus, at which neurodegenerative changes were detected, loss of coordination was revealed, especially between BiP and either of GRP94 or calnexin which indicates that de-coordination rather than aberrant expression is linked to deregulation of the UPR in aging. These findings underscore the involvement of UPR in the onset of aging-related pathologies and suggest that beyond levels of expression, concerted activation may be of significance to attain homeostasis. These findings emphasize the value of genetically diverse models and suggest that beyond levels of expression of individual targets the coordination of transcriptional networks should be considered when links to pathology are explored.

MeSH Terms

-

Keywords

Aging; ER stress; Peromyscus

Assessing the Accessibility of Content for Geriatric Fellowship Programs.

Abstract

The information available on program websites concerning geriatric fellowships in internal medicine and family medicine is a crucial factor in generating applicants' interest in individual programs. Our study aimed to quantify the accessibility and quality of information available on accredited geriatric (family medicine and internal medicine) fellowship program websites and further analyze the implications of the results obtained. A list of geriatric (family medicine and internal medicine) fellowship programs was analyzed through quantified measures after being verified for accreditation. Certain criteria were evaluated for each of these programs, such as website accessibility and whether critical information was available on online program websites. These criteria were centered on academic, administrative, and application-based factors. Hundred and fifty eight Family Medicine and Internal Medicine geriatric fellowship programs were identified in total, of which only 150 were accredited by the Accreditation Council for Graduate Medical Education and considered for analysis. Of these, 20 (13.33%) programs had website links that were nonfunctional and only 145 programs had websites at all. On programs' websites, information regarding aspects such as contact information-including phone number or email for the program-were lacking. Other information regarding past and current fellows, research, and curriculum were also generally lacking. Geriatric Fellowship websites in Family Medicine and Internal Medicine can gain better traction from those interested in applying for their programs by updating information more often and providing more and better information concerning critical aspects of the programs themselves online.

MeSH Terms

-

Keywords

accessibility; fellowship content; geriatrics

Where does cellular senescence belong in the pathophysiology of ovarian cancer?

Abstract

Although ovarian cancer is the leading cause of death from gynecological malignancies, there are still some issues that hamper accurate interpretation of the complexity of cellular and molecular events underlying the pathophysiology of this disease. One of these is cellular senescence, which is the process whereby cells irreversibly lose their ability to divide and develop a phenotype that fuels a variety of age-related diseases, including cancer. In this review, various aspects of cellular senescence associated with intraperitoneal ovarian cancer metastasis are presented and discussed, including mechanisms of senescence in normal peritoneal mesothelial cells; the role of senescent mesothelium in ovarian cancer progression; the effect of drugs commonly used as first-line therapy in ovarian cancer patients on senescence of normal cells; mechanisms of spontaneous senescence in ovarian cancer cells; and, last but not least, other pharmacologic strategies to induce senescence in ovarian malignancies. Collectively, this study shows that cellular senescence is involved in several aspects of ovarian cancer pathobiology. Proper understanding of this phenomenon, particularly its clinical relevance, seems to be critical for oncology patients from both therapeutic and prognostic perspectives.

MeSH Terms

-

Keywords

cancer metastasis; cellular senescence; ovarian cancer; peritoneal mesothelial cells; tumor microenvironment

[Metabolic syndrome as a gerontological problem (literature review).]

Abstract

Metabolic syndrome is a complex of interrelated disorders of carbohydrate and fat metabolism, as well as mechanisms for regulating blood pressure and endothelial function, which are based on a decrease in tissue sensitivity to insulin. Therefore, the leading component, pathophysiological basis and uniting factor of most of the symptoms described in metabolic syndrome is the resistance of peripheral tissues to the action of insulin, which is closely correlated with most metabolic disorders. It should be emphasized that almost all components of metabolic syndrome are established risk factors for developing cardiovascular diseases. The likelihood of developing metabolic syndrome increases with age. The article discusses the possibility of presenting the metabolic syndrome as a gerontological problem.

MeSH Terms

-

Keywords

aging; gerontology; metabolic syndrome; pathogenesis

Visualization of Guideline-Based Decision Support for the Management of Pressure Ulcers in Nursing Homes.

Abstract

Though a preventable risk, the management of pressure ulcers (PUs) in nursing homes is not satisfactory due to inadequate prevention and complex care plans. PUs early detection and wound assessment require to know the patient condition and risk factors and to have a good knowledge of best practices. We built a guideline-based clinical decision support system (CDSS) for the prevention, the assessment, and the management of PUs. Clinical practice guidelines have been modeled as decision trees and formalized as IF-THEN rules to be triggered by electronic health record (EHR) data. From PU assessment yielded by the CDSS, we propose a synthetic visualization of PU current and previous stages as a gauge that illustrates the different stages of PU continuous evolution. This allows to display PU current and previous stages to inform health care professionals of PU updated assessment and support their evaluation of previously delivered care efficiency. The CDSS will be integrated in NETSoins nursing homes EHR where gauges for several health problems constitute a patient dashboard.

MeSH Terms

Decision Support Systems, Clinical

• Electronic Health Records
• Health Personnel
• Humans
• Nursing Homes
• Pressure Ulcer

Keywords

Clinical decision support system; clinical practice guidelines; geriatrics; information display; nursing homes; pressure ulcer

Is ergothioneine a 'longevity vitamin' limited in the American diet?

Abstract

There is mounting evidence for the potential for the natural dietary antioxidant and anti-inflammatory amino acid l-Ergothioneine (ERGO) to prevent or mitigate chronic diseases of aging. This has led to the suggestion that it could be considered a 'longevity vitamin.' ERGO is produced in nature only by certain fungi and a few other microbes. Mushrooms are, by far, the leading dietary source of ERGO, but it is found in small amounts throughout the food chain, most likely due to soil-borne fungi passing it on to plants. Because some common agricultural practices can disrupt beneficial fungus-plant root relationships, ERGO levels in foods grown under those conditions could be compromised. Thus, research is needed to further analyse the role agricultural practices play in the availability of ERGO in the human diet and its potential to improve our long-term health.

MeSH Terms

-

Keywords

Antioxidant; ERGO, Ergothioneine; ETT, ERGO transporter; Ergothioneine; Fungi; Longevity vitamin; Regenerative agriculture

Prevalence of Atrophic and Hypertrophic Skin Ageing Phenotypes: A UK-based Observational Study.

Abstract

---

MeSH Terms

-

Keywords

skin aging;  skin neoplasms; prevalence

Pathogen burden and leukocyte telomere length in the United States.

Abstract

Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999-2000) for individuals 20-49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (- 0.30 [95% CI: - 0.36, - 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

MeSH Terms

-

Keywords

Biological aging; Geroscience; Immunosenescence; Persistent infections; Telomere length

Reconfiguration of Directed Functional Connectivity Among Neurocognitive Networks with Aging: Considering the Role of Thalamo-Cortical Interactions.

Abstract

A complete picture of how subcortical nodes, such as the thalamus, exert directional influence on large-scale brain network interactions across age remains elusive. Using directed functional connectivity and weighted net causal outflow on resting-state fMRI data, we provide evidence of a comprehensive reorganization within and between neurocognitive networks (default mode: DMN, salience: SN, and central executive: CEN) associated with age and thalamocortical interactions. We hypothesize that thalamus subserves both modality-specific and integrative hub role in organizing causal weighted outflow among large-scale neurocognitive networks. To this end, we observe that within-network directed functional connectivity is driven by thalamus and progressively weakens with age. Secondly, we find that age-associated increase in between CEN- and DMN-directed functional connectivity is driven by both the SN and the thalamus. Furthermore, left and right thalami act as a causal integrative hub exhibiting substantial interactions with neurocognitive networks with aging and play a crucial role in reconfiguring network outflow. Notably, these results were largely replicated on an independent dataset of matched young and old individuals. Our findings strengthen the hypothesis that the thalamus is a key causal hub balancing both within- and between-network connectivity associated with age and maintenance of cognitive functioning with aging.

MeSH Terms

-

Keywords

directed functional connectivity; healthy aging; multivariate Granger causality; salience network; thalamus; weighted net causal outflow

Association between physical disability and incidence of depressive symptoms in older Mexican adults

Abstract

Introduction: Functional limitations associated with the aging process can lead to the development of depressive symptoms and increase the vulnerability of older adults. Objective: To estimate the association between physical disability and the incidence of clinically significant depressive symptoms in older Mexican adults. Materials and methods: We conducted a retrospective cohort study with data from the Encuesta Nacional sobre Salud y Envejecimiento en México (ENASEM). The analytical sample (n=6,780) included adults over 50 years old with measurements for the main variables and no clinically significant depressive symptoms reported in the first round. These symptoms were evaluated with the CESD-9 scale and disability by means of the report of activities of daily living (ADL) or instrumental activities of daily living (IADL). Descriptive, bivariate, and multivariate analyses were performed using logistic regression models adjusted by sociodemographic variables, health conditions, childhood adversities, social participation, and stressful life events. Results: The incidence of clinically significant depressive symptoms was 25.75% (95% CI: 24,70 - 26,80). Compared to those without IADL limitations, an increased risk of 68% for the development of clinically significant depressive symptoms was found (95% CI: 1.10-2.57; p= 0,015). With the ADL model, the OR for the development of clinically significant depressive symptoms was 1.36 (1.01 -1.81; p= 0.039). Both models were adjusted by confounding variables. Conclusion: Presenting limitations in daily life is an important risk factor for the development of clinically significant depressive symptoms at two years of follow-up.

MeSH Terms

-

Keywords

Aged; disabled persons; depression; disability evaluation; incidence; aging; longitudinal studies; México

Transcriptomic Profiling of Human Pluripotent Stem Cell-derived Retinal Pigment Epithelium over Time.

Abstract

Human pluripotent stem cell (hPSC)-derived progenies are immature versions of cells, presenting a potential limitation to the accurate modelling of diseases associated with maturity or age. Hence, it is important to characterise how closely cells used in culture resemble their native counterparts. In order to select appropriate time points of retinal pigment epithelium (RPE) cultures that reflect native counterparts, we characterised the transcriptomic profiles of the hPSC-derived RPE cells from 1- and 12-month cultures. We differentiated the human embryonic stem cell line H9 into RPE cells, performed single-cell RNA-sequencing of a total of 16,576 cells to assess the molecular changes of the RPE cells across these two culture time points. Our results indicate the stability of the RPE transcriptomic signature, with no evidence of an epithelial-mesenchymal transition, and with the maturing populations of the RPE observed with time in culture. Assessment of Gene Ontology pathways revealed that as the cultures age, RPE cells upregulate expression of genes involved in metal binding and antioxidant functions. This might reflect an increased ability to handle oxidative stress as cells mature. Comparison with native human RPE data confirms a maturing transcriptional profile of RPE cells in culture. These results suggest that long-term in vitro culture of RPE cells allows the modelling of specific phenotypes observed in native mature tissues. Our work highlights the transcriptional landscape of hPSC-derived RPE cells as they age in culture, which provides a reference for native and patient samples to be benchmarked against.

MeSH Terms

-

Keywords

Aging; Human embryonic stem cell; Human pluripotent stem cell; Retinal pigment epithelium; Single-cell RNA sequencing

Season-of-birth phenomenon in health and longevity: epidemiologic evidence and mechanistic considerations.

Abstract

In many human populations, especially those living in regions with pronounced climatic differences between seasons, the most sensitive (prenatal and neonatal) developmental stages occur in contrasting conditions depending on the season of conception. The difference in prenatal and postnatal environments may be a factor significantly affecting human development and risk for later life chronic diseases. Factors potentially contributing to this kind of developmental programming include nutrition, outdoor temperature, infectious exposures, duration of sunlight, vitamin D synthesis, etc. Month of birth is commonly used as a proxy for exposures which vary seasonally around the perinatal period. Season-of-birth patterns have been identified for many chronic health outcomes. In this review, the research evidence for the seasonality of birth in adult-life disorders is provided and potential mechanisms underlying the phenomenon of early life seasonal programming of chronic disease and longevity are discussed.

MeSH Terms

-

Keywords

DOHaD; developmental programming; disease risk; longevity; seasonality of birth

Effects of Caloric Restriction on the Antagonistic and Integrative Hallmarks of Aging.

Abstract

Aging is a significant risk factor for cognitive decline associated with neurodegenerative diseases, which makes understanding what promotes 'healthy brain aging' very important. Studies suggest that caloric restriction (CR) is a non-genetic intervention that reliably extends life- and healthspan. Here, we review the CR literature related to both the subject of aging and alterations in cell cycle machinery, especially surrounding the regulation of the E2F/DP1 complex, to elucidate the cellular protection mechanisms in the brain induced via dietary applications. The alterations extending lifespan via CR appear to exert their effects by promoting survival of individual cells, downregulating cell proliferation, and inducing stem cell quiescence, which results in keeping the stem cell reserve for extreme needs. This survival instinct of cells is believed to cause some molecular adaptations for their maintenance of the system. Avoiding energy waste of proliferation machinery promotes the long term survival of the individual cells and this is due to adaptations to the limited nutrient supply in the environment. Such a protective mechanism induced by diet could be promoted via the downregulation of crucial cell cycle-related transcription activators. This review article aims to bring attention to the importance of molecular adaptations induced by diet that promote healthy brain aging. It will provide insights into alternative targets for new treatments or neuroprotective approaches against neurodegenerative pathophysiologies.

MeSH Terms

-

Keywords

Aging; Brain; Calorie Restriction; Cell Cycle; Neuroinflammation

Alteration of the Intra- and Inter-Lobe Connectivity of the Brain Structural Network in Normal Aging.

Abstract

The morphological changes in cortical parcellated regions during aging and whether these atrophies may cause brain structural network intra- and inter-lobe connectivity alterations are subjects that have been minimally explored. In this study, a novel fractal dimension-based structural network was proposed to measure atrophy of 68 parcellated cortical regions. Alterations of structural network parameters, including intra- and inter-lobe connectivity, were detected in a middle-aged group (30-45 years old) and an elderly group (50-65 years old). The elderly group exhibited significant lateralized atrophy in the left hemisphere, and most of these fractal dimension atrophied regions were included in the regions of the "last-in, first-out" model. Globally, the elderly group had lower modularity values, smaller component size modules, and fewer bilateral association fibers. They had lower intra-lobe connectivity in the frontal and parietal lobes, but higher intra-lobe connectivity in the temporal and occipital lobes. Both groups exhibited similar inter-lobe connecting pattern. The elderly group revealed separations, sparser long association fibers, commissural fibers, and lateral inter-lobe connectivity lost effect, mainly in the right hemisphere. New wiring and reconfiguring modules may have occurred within the brain structural network to compensate for connectivity, decreasing and preventing functional loss in cerebral intra- and inter-lobe connectivity.

MeSH Terms

-

Keywords

aging; brain structural network; inter-lobe connectivity; intra-lobe connectivity

Racial Discrimination and Telomere Length in Midlife African American Women: Interactions of Educational Attainment and Employment Status.

Abstract

Over the life course, African American (AA) women have faster telomere attrition, a biological indicator of accelerated aging, than White women. Race, sex, age, and composite socioeconomic status (SES) modify associations of institutional racial discrimination and telomere length. However, interactions with everyday racial discrimination have not been detected in AA women, nor have interactions with individual socioeconomic predictors. We estimated statistical interaction of institutional and everyday racial discrimination with age, education, employment, poverty, and composite SES on telomere length among midlife AA women. Data are from a cross-section of 140 AA women aged 30-50 years residing in the San Francisco Bay Area. Participants completed questionnaires, computer-assisted self-interviews, physical examinations, and blood draws. Adjusted linear regression estimated bootstrapped racial discrimination-relative telomere length associations with interaction terms. Racial discrimination did not interact with age, poverty, or composite SES measures to modify associations with telomere length. Interactions between independent SES variables were nonsignificant for everyday discrimination whereas institutional discrimination interacted with educational attainment and employment status to modify telomere length. After adjusting for covariates, we found that higher institutional discrimination was associated with shorter telomeres among employed women with lower education (β = -0.020; 95% confidence interval = -0.036, -0.003). Among unemployed women with higher education, higher institutional discrimination was associated with longer telomeres (β = 0.017; 95% confidence interval = 0.003, 0.032). Factors related to having a post-high school education may be protective against the negative effects of institutional racism on cellular aging for AA women.

MeSH Terms

-

Keywords

African Americans; Aging; Educational status; Employment; Telomeres; Women’s Health

Mitochondrial misreading in skeletal muscle accelerates metabolic aging and confers lipid accumulation and increased inflammation.

Abstract

We have recently reported on an experimental model of mitochondrial mistranslation conferred by amino acid exchange V338Y in the mitochondrial ribosomal protein MrpS5. Here we used a combination of RNA-Seq and metabolic profiling of homozygous transgenic MrpS5V338Y/V338Y mice to analyze the changes associated with the V338Y mutation in post-mitotic skeletal muscle. Metabolic profiling demonstrated age-dependent metabolic changes in the mutant V338Y animals, which included enhanced levels of age-associated metabolites and which were accompanied by increased glycolysis, lipid desaturation and eicosanoid biosynthesis, and alterations of the pentose phosphate pathway. In addition, transcriptome signatures of aged V338Y mutant muscle pointed to elevated inflammation, likely reflecting the increased levels of bioactive lipids. Our findings indicate that mistranslation-mediated chronic impairment of mitochondrial function affects specific bioenergetic processes in muscle in an age-dependent manner.

MeSH Terms

-

Keywords

Aging; Metabolome; Misreading; Mitochondria; Skeletal Muscle

Astaxanthin alleviates pathological brain aging through the upregulation of hippocampal synaptic proteins.

Abstract

Oxidative stress is currently considered to be the main cause of brain aging. Astaxanthin can improve oxidative stress under multiple pathological conditions. It is therefore hypothesized that astaxanthin might have therapeutic effects on brain aging. To validate this hypothesis and investigate the underlying mechanisms, a mouse model of brain aging was established by injecting amyloid beta (Aβ)25-35 (5 μM, 3 μL/injection, six injections given every other day) into the right lateral ventricle. After 3 days of Aβ injections, the mouse models were intragastrically administered astaxanthin (0.1 mL/d, 10 mg/kg) for 30 successive days. Astaxanthin greatly reduced the latency to find the platform in the Morris water maze, increased the number of crossings of the target platform, and increased the expression of brain-derived neurotrophic factor, synaptophysin, sirtuin 1, and peroxisome proliferator-activated receptor-γ coactivator 1α. Intraperitoneal injection of the sirtuin 1 inhibitor nicotinamide (500 μM/d) for 7 successive days after astaxanthin intervention inhibited these phenomena. These findings suggest that astaxanthin can regulate the expression of synaptic proteins in mouse hippocampus through the sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α signaling pathway, which leads to improvements in the learning, cognitive, and memory abilities of mice. The study was approved by the Animal Ethics Committee, China Medical University, China (approval No. CMU2019294) on January 15, 2019.

MeSH Terms

-

Keywords

brain aging; cognitive; factor; hippocampus; learning; memory; oxidative stress; pathways; synapse

How Does SARS-CoV-2 Affect the Central Nervous System? A Working Hypothesis.

Abstract

Interstitial pneumonia was the first manifestation to be recognized as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, in just a few weeks, it became clear that the coronavirus disease-2019 (COVID-19) overrun tissues and more body organs than just the lungs, so much so that it could be considered a systemic pathology. Several studies reported the involvement of the conjunctiva, the gut, the heart and its pace, and vascular injuries such as thromboembolic complications and Kawasaki disease in children and toddlers were also described. More recently, it was reported that in a sample of 214 SARS-CoV-2 positive patients, 36.4% complained of neurological symptoms ranging from non-specific manifestations (dizziness, headache, and seizures), to more specific symptoms such hyposmia or hypogeusia, and stroke. Older individuals, especially males with comorbidities, appear to be at the highest risk of developing such severe complications related to the Central Nervous System (CNS) involvement. Neuropsychiatric manifestations in COVID-19 appear to develop in patients with and without pre-existing neurological disorders. Growing evidence suggests that SARS-CoV-2 binds to the human Angiotensin-Converting Enzyme 2 (ACE2) for the attachment and entrance inside host cells. By describing ACE2 and the whole Renin Angiotensin Aldosterone System (RAAS) we may better understand whether specific cell types may be affected by SARS-CoV-2 and whether their functioning can be disrupted in case of an infection. Since clear evidences of neurological interest have already been shown, by clarifying the topographical distribution and density of ACE2, we will be able to speculate how SARS-CoV-2 may affect the CNS and what is the pathogenetic mechanism by which it contributes to the specific clinical manifestations of the disease. Based on such evidences, we finally hypothesize the process of SARS-CoV-2 invasion of the CNS and provide a possible explanation for the onset or the exacerbation of some common neuropsychiatric disorders in the elderly including cognitive impairment and Alzheimer disease.

MeSH Terms

-

Keywords

ACE2; Alzheimer disease; Ang(1-7)/Mas; COVID-19; RAAS; SARS-CoV; brain aging; neurodegenerative and psychiatric disorders abstract

Long-Term Stability of a RAFT-Modified Bulk-Fill Resin-Composite under Clinically Relevant Versus ISO-Curing Conditions.

Abstract

The addition of RAFT (reversible addition-fragmentation chain transfer) agents to the matrix formulation of a bulk-fill resin composite can significantly decrease the required curing time down to a minimum of 3 s. Evaluating the long term-stability of this resin composite in relation to varied curing conditions in an in-vitro environment was this study's goal. Specimens were produced according to either an ISO or one of two clinical curing protocols and underwent a maximum of three successive aging procedures. After each one of the aging procedures, 30 specimens for each curing condition were extracted for a three-point bending test. Fragments were then stereo-microscopically characterized according to their fracture mechanism. Weibull analysis was used to quantify the reliability of each aging and curing combination. Selected fragments ([i]n[/i] = 12) underwent further testing via depth-sensing indentation. Mechanical values for either standardized or clinical curing were mostly comparable. However, changes in fracture mechanism and Weibull modulus were observed after each aging procedure. The final procedure exposed significant differences in the mechanical values due to curing conditions. Curing conditions with increased radiant exposure seemingly result in a higher crosslink in the polymer-matrix, thus increasing resistance to aging. Yet, the clinical curing conditions still resulted in acceptable mechanical values, proving the effectiveness of RAFT-polymerization.

MeSH Terms

-

Keywords

RAFT-polymerization; Weibull analysis; accelerated aging; bulk-fill resin composite; curing conditions; depth-sensing indentation; fractography; long term-stability; three-point bending test

Clinical and Neuropsychological Correlates of Prefrailty Syndrome.

Abstract

Physical frailty is closely associated with cognitive impairment. We aim to investigate the neuropsychological profiles of prefrail and non-frail dementia-free community-dwelling older adults using a comprehensive neuropsychological evaluation, and to examine the association between specific frailty criteria and clinical and neuropsychological scores. Participants completed a comprehensive standardized neuropsychological evaluation (covering cognitive domains such as memory, executive functions, language and attention), and frailty assessment. Frailty was assessed according to biological criteria: unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. The sample comprised 60 dementia-free community-dwelling adults, aged 65 years or older (range 65-89 years; 60.0% women). Forty-two participants were classified as robust (no frailty criteria present), and 18 as prefrail (1 or 2 frailty criteria present). We explored neurocognitive differences between the groups and examined the association between specific criteria of frailty phenotype and clinical and neuropsychological outcomes with bivariate tests and multivariate models. Prefrail participants showed poorer cognitive performance than non-frail participants in both memory and non-memory cognitive domains. However, delayed episodic memory was the only cognitive subdomain that remained significant after controlling for age, gender, and educational level. Gait speed was significantly associated with general cognitive performance, immediate memory, and processing speed, while grip strength was associated with visual episodic memory and visuoconstructive abilities. Both gait speed and grip strength were negatively associated with depressive scores. Our results suggest that prefrailty is associated with cognitive dysfunction. The fact that specific cognitive domains may be susceptible to subclinical states of physical frailty may have important clinical implications. Indeed, early detection of specific cognitive dysfunctions may allow opportunities for reversibility.

MeSH Terms

-

Keywords

aging; gait speed; grip strength; neuropsychologial assessment; prefrailty

[State of autonomic regulation of heart rhythm in young and aged rats before and after application of different regimens of rhythmic extreme cooling.]

Abstract

The influence of various rhythmic extreme cold effects on the state of autonomic regulation of heart rate in young and aged rats was studied. According to the spectral analysis of heart rate variability, it has been found that in young rats, using rhythmic extreme cold exposures (RECE) temperature regimens of (-120 °С; -120 °С; -120 °С) and (-60 °С; -120 °С; -120 °С) significantly increased adaptive capabilities of the body due to the activation of its own homeostatic regulatory systems. At the same time, the combined regimen of RECE (-60 °С; 120 °С; -120 °С) occurred to be the most optimal for aged animals, since its use was not accompanied with an excessive activation of sympathoadrenal system at the early stages of experimental studies, in contrast to the regimen (120 °С; -120 °С; -120 °С). In addition, the use of this cooling mode contributed to a statistically significant increase in the total power of spectrum of neurohumoral regulation not so much due to a rise in activity of humoral-metabolic regulation link, the prevalence of which is characteristic of an old age, but due to an increase in the tone of vegetative centers, herewith the parasympathetic effects on the myocardium prevailed sympathetic ons.

MeSH Terms

-

Keywords

aging; autonomic nervous system; extreme rhythmic cold effects; heart rate variability

Personalized nutrition and healthy aging.

Abstract

The human lifespan and quality of life depend on complex interactions among genetic, environmental, and lifestyle factors. Aging research has been remarkably advanced by the development of high-throughput "omics" technologies. Differences between chronological and biological ages, and identification of factors (eg, nutrition) that modulate the rate of aging can now be assessed at the individual level on the basis of telomere length, the epigenome, and the metabolome. Nevertheless, the understanding of the different responses of people to dietary factors, which is the focus of precision nutrition research, remains incomplete. The lack of reliable dietary assessment methods constitutes a significant challenge in nutrition research, especially in elderly populations. For practical and successful personalized diet advice, big data techniques are needed to analyze and integrate the relevant omics (ie, genomic, epigenomic, metabolomics) with an objective and longitudinal capture of individual nutritional and environmental information. Application of such techniques will provide the scientific evidence and knowledge needed to offer actionable, personalized health recommendations to transform the promise of personalized nutrition into reality.

MeSH Terms

-

Keywords

aging; biological age; nutrition; omics; personalized nutrition; precision nutrition

Biostimulant Effects of Glutacetine® and Its Derived Formulations Mixed With N Fertilizer on Post-heading N Uptake and Remobilization, Seed Yield, and Grain Quality in Winter Wheat.

Abstract

Biostimulants could play an important role in agriculture particularly for increasing N fertilizer use efficiency that is essential for maintaining both yield and grain quality in bread wheat, which is a major global crop. In the present study, we examined the effects of mixing urea-ammonium-nitrate fertilizer (UAN) or urea with five new biostimulants containing Glutacetine® or its derivative formulations (VNT1, 2, 3, and 4) on the physiological responses, agronomic traits, and grain quality of winter wheat. A first experiment under greenhouse conditions showed that VNT1, VNT3, and VNT4 significantly increased the seed yield and grain numbers per ear. VNT4 also enhanced total plant nitrogen (N) and total grain N, which induced a higher N Harvest Index (NHI). The higher post-heading N uptake (for VNT1 and VNT4) and the acceleration of senescence speed with all formulations enabled better nutrient remobilization efficiency, especially in terms of N mobilization from roots and straw toward the grain with VNT4. The grain ionome was changed by the formulations with the bioavailability of iron improved with the addition of VNT4, and the phytate concentrations in flour were reduced by VNT1 and VNT4. A second experiment in three contrasting field trials confirmed that VNT4 increased seed yield and N use efficiency. Our investigation reveals the important role of these new formulations in achieving significant increases in seed yield and grain quality.

MeSH Terms

-

Keywords

Triticum aestivum; grain quality; iron bioavailability; nitrogen fertilizer; nitrogen remobilization; phytate; plant biostimulants; senescence

Prevalence of lifetime nonmedical opioid use among U.S. Health Center Patients aged 45 years and older with psychiatric disorders.

Abstract

Despite recent concerns over the increase in opioid misuse among aging adults, little is known about the prevalence of lifetime nonmedical opioid use in underserved, vulnerable middle-aged and older patients with psychiatric disorders. This study aims to determine the lifetime prevalence of nonmedical opioid use among underserved, vulnerable U.S. adults aged ≥45 years with psychiatric disorders. A nationally representative sample ([i]n[/i] = 3,294) was obtained from the 2014 Health Center Patient Survey which collects data on psychiatric disorders, opioid use, and other health information from underserved, vulnerable U.S. primary care populations. Predictor variables included self-reported panic disorder, generalized anxiety disorder, schizophrenia, or bipolar disorder. The outcome variable was self-reported lifetime nonmedical opioid use. Frequencies, counts, and unadjusted and adjusted logistic regression models were conducted with the cross-sectional survey dataset. Patients with bipolar disorder had the highest lifetime nonmedical opioid use rate (20.8%), followed by schizophrenia (19.3%), panic disorder (16.5%), and generalized anxiety disorder (14.5%). Nonmedical opioid use was significantly associated with bipolar disorder (OR 3.46, 95% CI [1.33, 8.99]) and generalized anxiety disorder (OR 2.03 95% CI [1.08, 3.83]). Our findings demonstrate a high prevalence of lifetime nonmedical opioid use in underserved, vulnerable middle-aged and older health center patients with psychiatric disorders. Given the prevalence, health center professionals should monitor, prevent, and treat new or reoccurring signs and symptoms of nonmedical opioid use in this high-risk group of aging patients with psychiatric disorders.

MeSH Terms

-

Keywords

Opioids; epidemiology; geriatric psychiatry; geriatrics; health centers; primary care

Naringenin alleviates nonalcoholic steatohepatitis in middle-aged Apoe mice: role of SIRT1.

Abstract

Naringenin is naturally isolated from citrus fruits possessing many pharmacological activities. However, little is known about the effect of naringenin on nonalcoholic steatohepatitis (NASH) in the model of metabolic syndrome. The present study is aimed to investigate the effect of naringenin on NASH in 12-mo-old male ApoE mice and its possible underlying mechanism. In vivo, 12-mo-old male ApoE mice were administrated with naringenin by intragastric gavage for 12 weeks. At the end of experiment, the blood samples and liver tissues were collected. Metabolic parameters in serum, levels of triglyceride, cholesterol and hydroxyproline, activities of antioxidant enzymes, and content of inflammatory cytokines (TNF-α and IL-6) in liver were examined by corresponding assay kits. Pathological changes in liver were observed by hematoxylin-eosin, oil red O, masson's trichrome, picro-sirius red and senescence β-galactosidase staining. Dihydroethidium was used for detection of reactive oxygen species (ROS). In vitro, AML-12 cells were treated with oleic acid in the presence or absence of naringenin for 24 h. Transfection of SIRT1 siRNA was also conducted in vitro. Lipid accumulation, cellular ROS generation, malondialdehyde content, antioxidant enzyme activities and secretion levels of TNF-α and IL-6 were examined. Both in vivo and in vitro, gene expressions were detected by real-time PCR or western blot. Naringenin administration improved metabolic parameters, suppressed hepatic steatosis, regulated expression of genes involved in lipid metabolism (FASN, SCD1, PPARα and CPT1α), reduced hepatic fibrosis and cell senescence, inhibited hepatic inflammation as evidenced by the decreased macrophage recruitment and content of TNF-α and IL-6, and reduced hepatic oxidative stress by suppressing ROS generation and normalizing activities of antioxidant enzymes. Notably, naringenin administration increased hepatic SIRT1 protein expression and activity along with the increased deacetylation of liver kinase B1 (LKB1), PGC1α and NF-κB. In vitro study, the benefits of naringenin on lipid accumulation, oxidative stress and inflammation were diminished by SIRT1 siRNA transfection. These results indicate that naringenin administration may be a potential curative therapy for NASH treatment and the activation of hepatic SIRT1-mediated signaling cascades is involved in its beneficial effects.

MeSH Terms

-

Keywords

AML-12 cells; Aging; ApoE(−/−) mice; Naringenin; Nonalcoholic steatohepatitis; SIRT1

Divergences in the control of mitochondrial respiration are associated with lifespan variation in marine bivalves.

Abstract

The role played by mitochondrial function in the aging process has been a subject of intense debate in the past few decades, as part of the efforts to understand the mechanistic basis of longevity. The mitochondrial oxidative stress theory of aging (MOSTA) suggests that a progressive decay of this organelle's function leads to an exacerbation of oxidative stress, with deleterious impact on mitochondrial structure and DNA, ultimately promoting aging. Among the traits suspected to be associated with longevity is the variation in regulation of oxidative phosphorylation, potentially impacting the management of oxidative stress. Longitudinal studies using the framework of metabolic control analysis have shown age-related differences in flux control of respiration, but this approach has seldom been taken on a comparative scale. Using four species of marine bivalves exhibiting a large range of maximum lifespans (from 28y to 507y), we report lifespan-related differences in flux control at different steps of the electron transfer system. Increased longevity was characterized by a lower control by NADH- (complex I-linked) and Succinate- (complex II- linked) pathways, while respiration was strongly controlled by complex IV when compared to shorter-lived species. Complex III exterted a strong control over respiration in all species. Furthermore, high longevity was associated with higher citrate synthase activity, and lower ATP synthase activity. Relieving the control exerted by the electron entry pathways could be advantageous for reaching a higher longevity, leading to an increased control by complex IV, the final electron acceptor in the electron transfer system.

MeSH Terms

-

Keywords

Invertebrate; Longevity; Metabolism; Mitochondria

The combination of mitogenic stimulation and DNA damage induces chondrocyte senescence.

Abstract

Cellular senescence is a phenotypic state characterized by stable cell-cycle arrest, enhanced lysosomal activity, and the secretion of inflammatory molecules and matrix degrading enzymes. Senescence has been implicated in osteoarthritis (OA) pathophysiology; however, the mechanisms that drive senescence induction in cartilage and other joint tissues are unknown. While numerous physiological signals are capable of initiating senescence, one emerging theme is that damaged cells convert to senescence in response to sustained mitogenic stimulation. The goal of this study was to develop an in vitro articular cartilage explant model to investigate the mechanisms of senescence induction. This study utilized healthy cartilage derived from cadaveric equine stifles and human ankles. Explants were irradiated to initiate DNA damage, and mitogenic stimulation was provided through serum-containing medium and treatment with transforming growth factor β1 and basic fibroblastic growth factor. Readouts of senescence were a quantitative flow cytometry assay to detect senescence-associated β galactosidase activity (SA-β-gal), immunofluorescence for p16 and γH2AX, and qPCR for the expression of inflammatory genes. Human cartilage explants required both irradiation and mitogenic stimulation to induce senescence as compared to baseline control conditions (7.16% vs 2.34% SA-β-gal high, p = 0.0007). These conditions also resulted in chondrocyte clusters within explants, a persistent DNA damage response, increased p16, and gene expression changes. Treatment of cartilage explants with mitogenic stimuli in the context of cellular damage reliably induces high levels of SA-β-gal activity and other senescence markers, which provides a physiologically relevant model system to investigate the mechanisms of senescence induction.

MeSH Terms

-

Keywords

Aging; DNA damage; Osteoarthritis; SA-β-gal; TGF- β1; bFGF

The price of longevity.

Abstract

---

MeSH Terms

-

Keywords

ataxin-3; autophagy; longevity; proteostasis; ubiquitin

Effects of Aging, Long-Term and Lifelong Exercise on the Urinary Metabolic Footprint of Rats.

Abstract

Life expectancy has risen in the past decades, resulting in an increase in the number of aged individuals. Exercise remains one of the most cost-effective treatments against disease and the physical consequences of aging. The purpose of this research was to investigate the effects of aging, long-term and lifelong exercise on the rat urinary metabolome. Thirty-six male Wistar rats were divided into four equal groups: exercise from 3 to 12 months of age (A), lifelong exercise from 3 to 21 months of age (B), no exercise (C), and exercise from 12 to 21 months of age (D). Exercise consisted in swimming for 20 min/day, 5 days/week. Urine samples collection was performed at 3, 12 and 21 months of life and their analysis was conducted by liquid chromatography-mass spectrometry. Multivariate analysis of the metabolite data did not show any discrimination between groups at any of the three aforementioned ages. However, multivariate analysis discriminated the three ages clearly when the groups were treated as one. Univariate analysis showed that training increased the levels of urinary amino acids and possibly protected against sarcopenia, as evidenced by the higher levels of creatine in the exercising groups. Aging was accompanied by decreased levels of urinary amino acids and signs of increased glycolysis. Concluding, both aging and, to a lesser degree, exercise affected the rat urinary metabolome, including metabolites related to energy metabolism, with exercise showing a potential to mitigate the consequences of aging.

MeSH Terms

-

Keywords

aging; exercise; liquid chromatography-mass spectrometry (LC/MS); urinary metabolites

Blood hormones and torque teno virus in peripheral blood mononuclear cells.

Abstract

Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects ([i]n[/i] = 27), we found presence of TTV in PMBC from 17.6% pre-MP ([i]n[/i] = 17), 25.0% post-MP ([i]n[/i] = 4) and 50.0% men ([i]n[/i] = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.

MeSH Terms

-

Keywords

Aging; Anovulatory; Commensal viruses; Estrogen; Hematology; Hypothyroidism; Immune response; Immunity; Immunodeficiency; Immunology; Infection; Infectious disease; Menstrual cycle; Microbiome; Reproductive hormone; Sex difference; Sex hormones; Steroid hormones; Viruses

Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia.

Abstract

In many tissues, stem cell (SC) proliferation is dynamically adjusted to regenerative needs. How SCs adapt their metabolism to meet the demands of proliferation and how changes in such adaptive mechanisms contribute to age-related dysfunction remain poorly understood. Here, we identify mitochondrial Ca uptake as a central coordinator of SC metabolism. Live imaging of genetically encoded metabolite sensors in intestinal SCs (ISCs) of Drosophila reveals that mitochondrial Ca uptake transiently adapts electron transport chain flux to match energetic demand upon proliferative activation. This tight metabolic adaptation is lost in ISCs of old flies, as declines in mitochondrial Ca uptake promote a "Warburg-like" metabolic reprogramming toward aerobic glycolysis. This switch mimics metabolic reprogramming by the oncogene Ras and enhances ISC hyperplasia. Our data identify a critical mechanism for metabolic adaptation of tissue SCs and reveal how its decline sets aging SCs on a metabolic trajectory reminiscent of that seen upon oncogenic transformation.

MeSH Terms

-

Keywords

Drosophila; Warburg; aging; calcium; cancer; intestine; metabolism; mitochondria; stem cell; tissue homeostasis

Entropic Approach to the Detection of Crucial Events.

Abstract

In this paper, we establish a clear distinction between two processes yielding anomalous diffusion and 1 / f noise. The first process is called Stationary Fractional Brownian Motion (SFBM) and is characterized by the use of stationary correlation functions. The second process rests on the action of crucial events generating ergodicity breakdown and aging effects. We refer to the latter as Aging Fractional Brownian Motion (AFBM). To settle the confusion between these different forms of Fractional Brownian Motion (FBM) we use an entropic approach properly updated to incorporate the recent advances of biology and psychology sciences on cognition. We show that although the joint action of crucial and non-crucial events may have the effect of making the crucial events virtually invisible, the entropic approach allows us to detect their action. The results of this paper lead us to the conclusion that the communication between the heart and the brain is accomplished by AFBM processes.

MeSH Terms

-

Keywords

crucial events; ergodicity breakdown; heart-brain communication; renewal aging; renewal processes; stationary correlation function

Patients with hip fracture and total hip arthroplasty surgery differ in anthropometric, but not cardiovascular screening abnormalities.

Abstract

With the rising number of hip surgeries, simple and cost-effective tools for surgery risk assessment are warranted. The analysis of heart rate variability (HRV) may not only provide critical insights into the general frailty of patients with hip surgery, but also allow for better differentiation of health profiles in different hip surgery groups. Using HRV analysis, the present study compared cardiovascular as well as anthropometric parameters between patients with hip surgery, the hip fracture surgery group (HFS) and the total hip arthroplasty group (THA), and a control group. 71 participants (56.3% women), aged 60-85 years, took part, divided into three groups-patients after hip surgery (21 HFS and 30 THA patients) and a control group (20 participants). Electrocardiogram was recorded at baseline and after the application of a physical stressor (grip strength). A 3 (group) × 2 (time) repeated measures ANOVA, and a chi square test were carried out to test for group differences. Higher weight (p = .002), body mass index (p = .001), and systolic blood pressure (p = .034) were found in THA patients compared to HFS patients. Lower calf circumference (p = .009) and diastolic blood pressure (p = .048) were observed for the HFS group compared to the control group. For cardiovascular parameters, significant differences emerged between the HFS group and the control group in HR (p = .005), SDNN (p = .034) and SD2 (p = .012). No significant differences in cardiovascular parameters were observed between the two hip surgery groups: neither at baseline nor during stressor recovery. While HRV seems to differentiate well between HFS patients and controls, more research with larger samples is needed to scrutinize similaritites and differences in cardiovascular profiles between HFS and THA patients.

MeSH Terms

-

Keywords

Aging; Cardiovascular reactivity; Heart rate variability; Hip fracture; Total hip arthroplasty

The chronic effects of CuO and ZnO nanoparticles on Eisenia fetida in relation to the bioavailability in aged soils.

Abstract

The bioavailability and bioaccumulation of metal-based engineered nanoparticles (ENPs) in soils need to be evaluated in environmentally relevant scenarios. The aim of this study was an analysis of potentially available metal-component ENPs (nano-ZnO and nano-CuO) in soils. Earthworms (Eisenia fetida) were used to examine the bioaccumulation potential of ENPs. Micro-particles (micro-ZnO and micro-CuO) and metal salts (ZnCl and CuCl ) were used to evaluate the nano-effect and the activity of dissolved ions, respectively. Zn- and Cu-compounds were added to sandy loam and silt loam at a concentration of 10 mg kg . The bioavailable fractions of metals were extracted from soil using H O, MgCl with CH COONa or EDTA. EDTA was the most effective extractant of Zn and Cu (10.06-11.65 mg Zn kg and 2.69-3.52 mg Cu kg ), whereas the H O-extractable metal concentration was at the lowest level (1.98-2.12 mg Zn kg and 0.54-0.82 Cu mg kg ). The bioavailable metal concentrations were significantly higher in silt loam than sandy loam soil, which was related to the higher pH value of silt. There were no significant differences between the Zn content in the earthworms incubated in the two soils, which may confirm the auto-regulation of the Zn content by earthworms. However, the bioaccumulation of Cu was strongly correlated with the extractable Cu concentrations. The juvenile earthworms accumulated Cu and Zn more than adults. Based on our results, aging neutralized the differences between the ionic and particulate effects of metal-compounds.

MeSH Terms

-

Keywords

Aging; Bioaccumulation; Bioavailability; Eisenia fetida; Engineered nanoparticles; Extractability

C1q/TNF-related protein-9 attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy.

Abstract

Autophagy is an important process in the pathogenesis of atherosclerosis. C1q/tumor necrosis factor-related protein 9 (CTRP9) is the closest adiponectin paralog. CTRP9 has anti-aging and anti-atherogenic effects, but its roles in autophagy and endothelial senescence are currently unknown. This study aimed to evaluate whether CTRP9 prevents palmitic acid (PA)-induced endothelial senescence by promoting autophagy. After no treatment or pre-treatment of human umbilical vein endothelial cells with CTRP9 prior to PA treatment, the level of senescence was measured by senescence associated acidic β-galactosidase staining and the level of hyperphosphorylated pRB protein. Autophagy was evaluated by LC3 conversion and the level of p62/SQSTM1, a protein degraded during autophagy. Autophagosome-lysosome fusion was detected by fluorescence microscopy. Pre-treatment with CTRP9 attenuated PA-induced endothelial senescence. CTRP9 increased the conversion of LC3-I to LC3-II and decreased p62 levels in a time- and dose-dependent manner. Although both CTRP9 and PA treatment increased LC3 conversion, treatment with PA increased the expression level of p62 and decreased the fusion of autophagosomes and lysosomes, which represented decreased autophagic flux. However, pre-treatment with CTRP9 recovered the autophagic flux inhibited by PA. AMP-activated kinase (AMPK) activation was involved in LC3 conversion and decreased p62 levels induced by CTRP9. CTRP9 inhibits PA-induced endothelial senescence by recovering autophagy and autophagic flux through AMPK activation.

MeSH Terms

-

Keywords

C1q/TNF-related protein-9; aging; atherosclerosis; autophagy; endothelial senescence

Healthy aging interventions reduce repetitive element transcripts.

Abstract

Transcripts from non-coding repetitive elements (RE) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. We analyze RE in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-⍺-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to a high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that: 1) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and a high-fat diet increase RE expression; and 2) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.

MeSH Terms

-

Keywords

Non-coding RNA; RNA-seq; healthspan; lifespan; transposable elements

Control of lifespan and survival by [i]Drosophila[/i] NF-κB signaling through neuroendocrine cells and neuroblasts.

Abstract

We report a comparative analysis of the effects of immune activation in the fly nervous system using genetic activation models to target [i]Drosophila[/i] NF-κB within Toll versus Imd pathways. Genetic gain-of-function models for either pathway pan-neuronally as well as in discrete subsets of neural cells including neuroendocrine insulin-producing cells (IPCs) or neuroblasts reduce fly lifespan, however, these phenotypes in IPCs and neuroblasts are stronger with Toll activation than Imd activation. Of note, while aging is influenced more by Toll/NF-κB activation in IPCs during adulthood, neuroblasts influence aging more substantially during development. The study then focused on Toll/NF-κB inhibition, revealing that IPCs or neuroblasts are important for the effects of lifespan and healthspan extension but in a life stage-dependent manner while some of these effects display sexual dimorphism. Importantly, co-inhibition of Toll/NF-κB pathway in IPCs and neuroblasts increased fly lifespan greater than either cell population, suggesting that independent mechanisms might exist. Toll/NF-κB inhibition in IPCs was also sufficient to enhance survival under various fatal stresses, supporting the additional benefits to fly healthspan. In conclusion, IPCs and neuroblasts are important for [i]Drosophila[/i] NF-κB for controlling lifespan.

MeSH Terms

-

Keywords

Drosophila; aging; brain; neuron

Methionine transsulfuration pathway is upregulated in long-lived humans.

Abstract

Available evidences point to methionine metabolism as a key target to study the molecular adaptive mechanisms underlying differences in longevity. The plasma methionine metabolic profile was determined using a LC-MS/MS platform to systematically define specific phenotypic patterns associated with genotypes of human extreme longevity (centenarians). Our findings demonstrate the presence of a specific plasma profile associated with human longevity characterized by an enhanced transsulfuration pathway and tricarboxylic acid (TCA) cycle intermediates, as well as a reduced content of specific amino acids. Furthermore, our work reveals that centenarians maintain a strongly correlated methionine metabolism, suggesting an improved network integrity, homeostasis and more tightly regulated metabolism. We have discovered a particular methionine signature related to the condition of extreme longevity, allowing the identification of potential mechanisms and biomarkers of healthy aging.

MeSH Terms

-

Keywords

Amino acids; Centenarians; Longevity; Methionine cycle; Plasma; TCA Cycle metabolites; Transsulfuration pathway

Mitochondrial Glutamine Metabolism Determines Senescence Induction After Chemotherapy.

Abstract

Cellular senescence is an important tumor-suppressive mechanism that arrests the cell cycle of damaged cells after diverse stresses. This study aimed to elucidate the role of mitochondrial glutamine (Gln) metabolism in senescence cell-fate decision after DNA damage. β-galactosidase staining was used to determine senescence induction. The mechanistic target of rapamycin (mTOR) activity and p21 expression were examined by western blot. Cell proliferation and clonogenic growth were evaluated. Inhibition of mitochondrial Gln metabolism suppressed DNA damage-induced senescence, whereas increased Gln anaplerosis resulted in a profound induction of senescence. Mechanistically, Gln anaplerosis mediated senescence induction by activating mTOR signaling upon DNA damage. Importantly, enhancing Gln anaplerosis could reduce the emergence of proliferative subpopulations of cancer cells after exposure to non-lethal doses of chemotherapeutic agents. Mitochondrial Gln metabolism is an important regulator of DNA damage-induced senescence, which may be used for developing effective therapeutic approaches.

MeSH Terms

-

Keywords

DNA damage; Senescence; glutamine metabolism; mTOR

Sleep medication use and incident dementia in a nationally representative sample of older adults in the US.

Abstract

Sleep difficulties are common among older adults, and clinical management of sleep difficulties commonly includes sleep medication (pharmacological and non-pharmacological). Our research examines sleep medication use and incident dementia over 8 years using nationally representative data from older adults ages 65 years and older in the United States. We used data collected from the National Health and Aging Trends Study (NHATS), a nationally-representative longitudinal study of Medicare beneficiaries. Routine sleep medication use (pharmacological and non-pharmacological) was defined as use "most nights" or "every night." Participants were screened for dementia with validated instruments that assessed memory, orientation, and executive function. We conduct prospective analyses to examine the relationship between routine sleep medication use and incident dementia using Cox proportional hazards modeling and estimated survival curves. Analyses controlled for age, sex, marital status, education, and chronic conditions. Among respondents at baseline (n = 6373), most participants (21%) were age 70-74 years of age. Participants were 59% female and the sample comprised non-Hispanic White (71%). At baseline, 15% of our study sample reported using sleep medication routinely, which is representative of 4.6 million older adults in the US. Covariate adjusted proportional hazard models revealed that routinely using sleep medication was associated with incident dementia (HR = 1.30, 95%CI: 1.10 to 1.53, p < 0.01). Our study observed, in a nationally representative study of older adults in the US across 8 years of data that 15% of older adults report routinely using sleep medication, yet routine use of sleeping medication was associated with incident dementia across the follow-up interval. Future research may examine behavioral approaches to improving sleep among older adults.

MeSH Terms

-

Keywords

Dementia; Gerontology; Sleep medication; Sleep medicine

Trends in inpatient discharges with drug or alcohol admission diagnoses to a skilled nursing facility among older adults, New York City 2008-2014.

Abstract

Recent research shows an increase in drug and alcohol-related hospitalizations in the USA, especially among older adults. However, no study examines trends in discharges to a skilled nursing facility (SNF) after a drug or alcohol-related hospitalization. Older adults are more likely to need post-hospital care in a SNF after a hospitalization due to an increased presence of chronic diseases and functional limitations. Therefore, the objective of this study was to estimate trends in drug or alcohol-related hospitalizations with discharge to a SNF among adults age 55 and older. We analyzed data from New York State's Statewide Planning and Research Cooperative System to calculate the number of cannabis, cocaine, opioid, and alcohol-related hospitalizations in New York City that resulted in discharge to a SNF from 2008 to 2014 among adults age 55 and older. Using New York City population estimates modified from US Census Bureau, we calculated age-specific rates per 100,000 adults. Trend tests were estimated using joinpoint regressions to calculate annual percentage change (APC) with 95% confidence intervals (CI) and stratified by adults age 55-64 and adults age 65 and older. During the study period, among adults age 55-64, there were significant increases in cocaine, cannabis, and opioid-related hospitalizations that resulted in discharge to a SNF. For adults ≥ 65 years, there were sharp increases across all substances with larger increases in opioids (APC of 10.66%) compared to adults 55-64 (APC of 6.49%). For both age groups and among the four substances, alcohol-related hospitalizations were the leading cause of discharge to a SNF. We found an increase in hospital discharges to SNFs for patients age 55 and older admitted with alcohol or drug-related diagnoses. Post-acute and long-term care settings should prepare to care for an increase in older patients with substance use disorders by integrating a range of harm reduction interventions into their care settings.

MeSH Terms

-

Keywords

Geriatrics; Long-term care; Post-acute care; Substance use

The effect of age on the acquisition and selection of cancer driver mutations in sun-exposed normal skin.

Abstract

The accumulation of somatic mutations contributes to ageing and cancer. Sunlight is the principal aetiological factor associated with skin cancer development. However, genetic and phenotypic factors also contribute to skin cancer risk. This study aimed at exploring the role of photoaging, as well as other well-known epidemiological risk factors, in the accumulation of somatic mutations in cancer-free human epidermis. We deeply sequenced 46 genes in normal skin biopsies from 127 healthy donors, from which phenotypic data (including age, pigmentation-related genotype and phenotype) and sun exposure habits were collected. We determined the somatic mutational burden, mutational signatures, clonal selection and frequency of driver mutations in all samples. Our results reveal an exponential accumulation of UV-related somatic mutations with age, matching skin cancer incidence. The increase of mutational burden is in turn modified by an individual's skin phototype. Somatic mutations preferentially accumulated in cutaneous squamous cell carcinoma (cSCC) cancer genes and clonally expanded with age, with distinct mutational processes underpinning different age groups. Our results suggest loss of fidelity in transcription-coupled repair later in life. Our findings reveal that aging is not only associated with an exponential increase in the number of somatic mutations accumulated in normal epidermis, but also with selection and expansion of cancer-associated mutations. Aged, sun-exposed normal skin is thus an extended mosaic of multiple clones with driver mutations, poised for the acquisition of transforming events.

MeSH Terms

-

Keywords

Aging; Next-generation sequencing; Skin Phototype; Somatic mutation; UV exposure; carcinogenesis; mutational spectrum; normal epidermis

Cyst Reduction by Melatonin in a Novel [i]Drosophila[/i] Model of Polycystic Kidney Disease.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the [i]Bicaudal C[/i] ([i]BicC[/i]) [i]Drosophila[/i] model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the [i]BicC[/i] fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment.

MeSH Terms

-

Keywords

Drosophila; longevity; melatonin; oxidative stress; polycystic kidney disease; renal cysts

Ozone-induced changes in oxidative stress parameters in brain regions of adult, middle-age, and senescent Brown Norway rats.

Abstract

A critical part of community based human health risk assessment following chemical exposure is identifying sources of susceptibility. Life stage is one such susceptibility. A prototypic air pollutant, ozone (O ) induces dysfunction of the pulmonary, cardiac, and nervous systems. Long-term exposure may cause oxidative stress (OS). The current study explored age-related and subchronic O -induced changes in OS in brain regions of rats. To build a comprehensive assessment of OS-related effects of O , a tripartite approach was implemented focusing on 1) the production of reactive oxygen species (ROS) [NADPH Quinone oxidoreductase 1, NADH Ubiquinone reductase] 2) antioxidant homeostasis [total antioxidant substances, superoxide dismutase, γ-glutamylcysteine synthetase] and 3) an assessment of oxidative damage [total aconitase and protein carbonyls]. Additionally, a neurobehavioral evaluation of motor activity was compared to these OS measures. Male Brown Norway rats (4, 12, and 24 months of age) were exposed to air or O (0.25 or 1 ppm) via inhalation for 6 h/day, 2 days per week for 13 weeks. A significant decrease in horizontal motor activity was noted only in 4-month old rats. Results on OS measures in frontal cortex (FC), cerebellum (CB), striatum (STR), and hippocampus (HIP) indicated life stage-related increases in ROS production, small decreases in antioxidant homeostatic mechanisms, a decrease in aconitase activity, and an increase in protein carbonyls. The effects of O exposure were brain area-specific, with the STR being more sensitive. Regarding life stage, the effects of O were greater in 4-month-old rats, which correlated with horizontal motor activity. These results indicate that OS may be increased in specific brain regions after subchronic O exposure, but the interactions between age and exposure along with their consequences on the brain require further investigation.

MeSH Terms

-

Keywords

Aging; Air pollution; Antioxidants; Neurotoxicity; Oxidative stress; Ozone; Protein carbonyls; Susceptibility

Molecular Mechanisms to Target Cellular Senescence in Hepatocellular Carcinoma.

Abstract

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer-related death and is the most common type of liver cancer. Due to the current paucity of drugs for HCC therapy there is a pressing need to develop new therapeutic concepts. In recent years, the role of Serum Response Factor (SRF) and its coactivators, Myocardin-Related Transcription Factors A and B (MRTF-A and -B), in HCC formation and progression has received considerable attention. Targeting MRTFs results in HCC growth arrest provoked by oncogene-induced senescence. The induction of senescence acts as a tumor-suppressive mechanism and therefore gains consideration for pharmacological interventions in cancer therapy. In this article, we describe the key features and the functional role of senescence in light of the development of novel drug targets for HCC therapy with a focus on MRTFs.

MeSH Terms

-

Keywords

DLC1; HCC; MRTF; SRF; senescence; senolytics

Triggering Postural Movements With Virtual Reality Technology in Healthy Young and Older Adults: A Cross-Sectional Validation Study for Early Dementia Screening.

Abstract

With the ultimate aim of early diagnosis of dementia, a new body balance assessment system with integrated head-mounted display-based virtual reality (VR) has been developed. We hypothesized that people would sway more in anterior-posterior (AP) direction when they were exposed to a VR environment where we intentionally provoked movements in forward and backward directions. A total of 14 healthy older adults (OA) (73.14±4.26 years) and 15 healthy young adults (YA) (24.93±1.49 years) were assessed for group differences in sway behavior. Body sway speed in 22 different conditions with and without VR environments was analyzed. Significant differences and large effect sizes were observed in AP sway under the VR environments (OA with [i]P[/i] < 0.02; effect size> 0.61, YA with [i]P[/i] < 0.003; effect size> 0.72) compared to the baseline condition without the VR environments. In addition, significant differences were found between the two groups in AP sway in all test conditions ([i]P[/i] < 0.01). Our study shows that a VR environment can trigger body sway in an expected direction, which may indicate that it is possible to enhance the sensitivity of balance assessment by integrating immersive VR environments. The result of this study warrants a cross-sectional study in which OA diagnosed with and without dementia are compared on their sway behavior.

MeSH Terms

-

Keywords

aging; balance assessment; dementia; early diagnosis; head-mounted display (HMD); postural sway; posture; virtual reality

Reduced erythrocyte lifespan measured by chromium-51 in patients with type 2 diabetes undergoing long-term hemodialysis.

Abstract

A reduced erythrocyte lifespan potentially explains the low hemoglobin A1c values found in hemodialysis patients. However, data supporting this notion in patients with type 2 diabetes is unclear. We evaluated the erythrocyte lifespan in patients with type 2 diabetes undergoing long-term hemodialysis and investigated potential predictors of erythrocyte lifespan. Long-term hemodialysis patients with type 2 diabetes and type 2 diabetes patients without nephropathy (estimated glomerular filtration rate > 60 mL/min/1.73 m ) were included. The erythrocyte lifespan was measured using chromium-51 ( Cr)-labeled erythrocytes. Blood radiotracer activity was measured six to nine times over a period of 3-5 weeks to determine the erythrocyte lifespan of each patient. Biochemical markers were obtained five times over 16 weeks and associated with the erythrocyte lifespan. Type 2 diabetes patients undergoing hemodialysis (N = 13) had a significantly shorter median erythrocyte lifespan of 49.7 (interquartile range [IQR] = 44.1-58.6) days compared with 64.2 (IQR = 62.6-83.5) days in the control group (N = 10) (P ˂ 0.001) with a difference between medians of 14.5 (95% confidence interval = 8.1-38.8) days. In the hemodialysis group, no association could be detected between the erythrocyte lifespan and markers of hemolysis, level of inflammation, or urea. A reduced erythrocyte lifespan was detected in type 2 diabetes patients undergoing long-term hemodialysis. This may contribute to the reduced hemoglobin A1c values observed in the type 2 diabetic hemodialysis population. An association could not be detected between the erythrocyte lifespan and biochemical markers of hemolysis or inflammation.

MeSH Terms

-

Keywords

Hemodialysis; chromium-51; erythrocyte lifespan; type 2 diabetes

Cell non-autonomous regulation of health and longevity.

Abstract

As the demographics of the modern world skew older, understanding and mitigating the effects of aging is increasingly important within biomedical research. Recent studies in model organisms demonstrate that the aging process is frequently modified by an organism's ability to perceive and respond to changes in its environment. Many well-studied pathways that influence aging involve sensory cells, frequently neurons, that signal to peripheral tissues and promote survival during the presence of stress. Importantly, this activation of stress response pathways is often sufficient to improve health and longevity even in the absence of stress. Here, we review the current landscape of research highlighting the importance of cell non-autonomous signaling in modulating aging from [i]C. elegans[/i] to mammals. We also discuss emerging concepts including retrograde signaling, approaches to mapping these networks, and development of potential therapeutics.

MeSH Terms

-

Keywords

C. elegans; D. melanogaster; aging; genetics; genomics; healthspan; insulin signaling; neuroscience; sensory perception

Handgrip strength asymmetry is associated with future falls in older Americans.

Abstract

Examining handgrip strength (HGS) asymmetry could extend the utility of handgrip dynamometers for screening future falls. We sought to determine the associations of HGS asymmetry on future falls in older Americans. The analytic sample included 10,446 adults aged at least 65 years from the 2006-2016 waves of the Health and Retirement Study. Falls were self-reported. A handgrip dynamometer measured HGS. The highest HGS on each hand was used for determining HGS asymmetry ratio: (non-dominant HGS/dominant HGS). Those with HGS asymmetry ratio < 1.0 had their ratio inverted to make all HGS asymmetry ratios ≥ 1.0. Participants were categorized into asymmetry groups based on their inverted HGS asymmetry ratio: (1) 0.0-10.0%, (2) 10.1-20.0%, (3) 20.1-30.0%, and (4) > 30.0%. Generalized estimating equations were used for the analyses. Every 0.10 increase in HGS asymmetry ratio was associated with 1.26 (95% confidence interval (CI) 1.07-1.48) greater odds for future falls. Relative to those with HGS asymmetry 0.0-10.0%, participants with HGS asymmetry > 30.0% had 1.15 (CI 1.01-1.33) greater odds for future falls; however, the associations were not significant for those with HGS asymmetry 10.1-20.0% (odds ratio: 1.06; CI 0.98-1.14) and 20.1-30.0% (odds ratio: 1.10; CI 0.99-1.22). Compared to those with HGS asymmetry 0.0-10.0%, participants with HGS asymmetry > 10.0% and > 20.0% had 1.07 (CI 1.01-1.16) and 1.12 (CI 1.02-1.22) greater odds for future falls, respectively. Asymmetric HGS, as a possible biomarker of impaired neuromuscular function, may help predict falls. We recommend that HGS asymmetry be considered in HGS protocols and fall risk assessments.

MeSH Terms

-

Keywords

Aging; Functional laterality; Geriatric assessment; Geriatrics; Muscle strength dynamometer

Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis.

Abstract

Phenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (T ) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases.

MeSH Terms

-

Keywords

CITE-seq; CNS; aging; brain; brain immunity; dysbiosis; gut microbiota; single-cell sequencing

Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish.

Abstract

Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival. Using senescence-associated β-galactosidase staining, we found that carbofuran accelerates the cellular senescence in spns1 mutant zebrafish. The yolk opaqueness, a premature ageing phenotype in zebrafish embryos, was accelerated by carbofuran treatment. In the survival study, carbofuran shortened the life span of spns1 mutant zebrafish. Autophagy is the cellular lysosomal degradation, usually up-regulated in the senescent cells. To know the impact of carbofuran exposure on autophagy progress, we established a double-transgenic zebrafish line, harbouring EGFP-tagged LC3-II and mCherry-tagged Lamp1 on spns1 mutant background, whereas we found, carbofuran exposure synergistically accelerates autolysosome formation with insufficient lysosome-mediated degradation. Our data collectively suggest that carbofuran exposure synergistically accelerates the cellular senescence and affects biological ageing in spns1 defective animals.

MeSH Terms

-

Keywords

carbofuran; life span; senescence; spinster homolog 1; zebrafish

Rationale and Methodology of The PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study [PIONEER].

Abstract

To describe the rationale, design and methodology of a geographically-representative and population-based study investigating the epidemiology, impact, personal and economic burden of age-related eye diseases, declining visual and other sensory systems in Asians aged >60 years in Singapore.PIONEER (The PopulatION HEalth and Eye Disease PRofilE in Elderly Singaporeans Study) is currently a cross-sectional study targeting 3152 Chinese, Malay and Indian adults who are Singapore citizens or permanent residents aged 60 years and older living across Singapore. The study is intended to be longitudinal, with several waves of data planned to be collected in the future. The sampling frame consisted of 7000 names derived from age, gender and ethnicity-stratified random sampling of individuals >60 years. Selected individuals were invited via letters, home visits, and telephone calls for a clinical assessment at the Singapore Eye Research Institute. Individuals with limited mobility were examined in a custom-designed mobile eye clinic. Questionnaires were subsequently administered at participants' homes by trained interviewers in their preferred language. A total of 3,299 participants (from East, West, North and South Singapore) were approached from December 2017 to November 2019. Of these, 953 (28.5%) were deemed ineligible. Out of 2,346 eligible participants, 904 (38.5%) refused, and 1,442 (61.5%) attended our clinical testing protocol, giving an initial response rate of 61.5%. Of these, 1,170 (81%) were cognitively able to complete the questionnaire assessment. The mean age±SD of our participants was 73.8±8.6 years; n=798 (55.3%) were female; and 828 (57.4%) were of Chinese ethnicity. The findings from this study will allow a deeper understanding of the risk factors and impact of aging in Asian populations, particularly in relation to the visual function and other functional system.

MeSH Terms

-

Keywords

aging; epidemiology; eye disease; population-based study; visual function system; visual impairment

Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans.

Abstract

Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, we found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin (DCN) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, DCN knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas DCN overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and DCN bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of [i]DCN[/i] gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased [i]DCN[/i] mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, decreased [i]DCN[/i] mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation. Thus, IGF-IR could be the prime target of aging in down-regulating the IGF-I signaling of bmMSCs, where DCN could be a critical mediator.

MeSH Terms

-

Keywords

IGF-I; aging; bone marrow mesenchymal stem cell; osteoporosis; small leucine-rich proteoglycan

[Potentials and limits of aging cohort studies for geriatric psychiatry].

Abstract

The sizeable number of population-based cohort studies of aging in Germany have provided highly valuable contributions for the specification of risk factors and predictors for frequent mental disorders in old age, especially dementia and depression. The results from these cohort studies enable the specification of mechanisms for the development of and preventative interventions for common mental disorders in old age. On the other hand, there is a significant paucity of clinical cohort studies investigating disease trajectories and possible markers for specific individualized interventions of frequent mental disorders in old age. In this article, we report selected key findings from cohort studies of aging and discuss novel approaches for the integration and harmonization of population-based and clinical cohort studies.

MeSH Terms

-

Keywords

Aging; Disease course; Mental diseases; Panel studies; Risk factors

Divergent Nodes of Non-autonomous UPR Signaling through Serotonergic and Dopaminergic Neurons.

Abstract

In multicellular organisms, neurons integrate a diverse array of external cues to affect downstream changes in organismal health. Specifically, activation of the endoplasmic reticulum (ER) unfolded protein response (UPR ) in neurons increases lifespan by preventing age-onset loss of ER proteostasis and driving lipid depletion in a cell non-autonomous manner. The mechanism of this communication is dependent on the release of small clear vesicles from neurons. We find dopaminergic neurons are necessary and sufficient for activation of cell non-autonomous UPR to drive lipid depletion in peripheral tissues, whereas serotonergic neurons are sufficient to drive protein homeostasis in peripheral tissues. These signaling modalities are unique and independent and together coordinate the beneficial effects of neuronal cell non-autonomous ER stress signaling upon health and longevity.

MeSH Terms

-

Keywords

UPRER; aging; non-autonomous signaling; stress response

Risk factors for emergency department revisit in elderly patients with gastrointestinal bleeding secondary to anticoagulant therapy.

Abstract

To evaluate the frequency of emergency department (ED) revisits among elderly patients with gastrointestinal bleeding secondary to anticoagulant treatment and identify factors associated with an increased risk of ED revisits. A 3-year retrospective observational study was designed, including elderly patients (≥65 years) with atrial fibrillation and undergoing oral anticoagulation therapy who visited the ED for gastrointestinal bleeding. To evaluate the risk factors for 30-day revisit, a multivariate analysis was designed including comorbidities, concomitant treatment, change in anticoagulant treatment and prescription of direct-acting oral anticoagulants. 80 patients were included. At discharge, anticoagulation therapy was modified in 21 (26.2%) patients; and changed from an oral anticoagulant to heparin in 17 (21.2%) patients and to another oral anticoagulant in 4 (5.0%) patients. Anticoagulant treatment was withdrawn in 5 (6.3%) patients at discharge. Eleven (13.7%) patients revisited the ED 30 days after hospital discharge for bleeding episodes. No differences in the frequency of revisit to the ED were observed in the patients who changed their anticoagulant treatment at discharge. In the multivariate analysis, chronic kidney disease was the only factor significantly associated with revisits at 30 days. Elderly patients who experience a first episode of gastrointestinal bleeding have a high risk of revisiting the ED for a bleeding episode, with no particular differences between the types of anticoagulant prescribed at discharge.

MeSH Terms

-

Keywords

anticoagulants; drug-related side effects and adverse reactions; emergency medicine; geriatrics; safety

Effect of Ag on Properties, Microstructure, and Thermostability of Cu-Cr Alloy.

Abstract

Cu-Cr-based alloys exhibit excellent electrical conductivity and strength, but their poor thermal stability limits their application in industry. In this paper, Cu-0.2Cr (at. %) and Cu-0.2Cr-0.12Ag (at. %) alloys were prepared to study the effect of Ag on the properties, microstructure, and thermal stability of the Cu-Cr alloy. Microstructure and precipitation were observed by an optical microscope (OM) and a transmission-electron microscope (TEM). After cold-drawing by 99.9% and aging at 450 °C for 2 h, the peak hardness and electric conductivity of the Cu-Cr alloy were 120.3 HV and 99.5% IACS, respectively, and those of the Cu-Cr-Ag alloy were 135.8 HV and 98.3% IACS, respectively. The softening temperature of the Cu-Cr alloy was 500~525 °C, and that of the Cu-Cr-Ag alloy was about 550 °C. The creep strains of the Cu-Cr and Cu-Cr-Ag alloys at 40 MPa and 400 ℃ for 50 h were 0.18% and 0.05%, respectively. Ag elements improved the thermal stability of the Cu-Cr alloy. Recovery and recrystallization occurred before the coarsening of precipitates during the softening process. Ag atoms mainly improved the softening resistance of the alloy by delaying recrystallization, and mainly increased creep resistance by preventing the increase in mobile-dislocation density.

MeSH Terms

-

Keywords

Cu–Cr system alloy; aging process; microstructure; physical properties; thermal stability

Trends in comorbidities among HIV-infected hospital admissions in New York City from 2006-2016.

Abstract

Due to the advent and success of antiretroviral therapy (ART), the number of people living and aging with HIV has grown substantially. Although PLHIV are experiencing longer life expectancies, this achievement may be undermined by increasing and disproportionate chronic disease burden among PLHIV. This study is a retrospective analysis of adult (≥18 years) inpatient hospital discharges from a large hospital system in the New York City, New York metropolitan area, between January 1st, 2006 and December 31st, 2016. We aimed to investigate 1) changes in the prevalence of Charlson-defined comorbidities among PLHIV hospitalized between 2006 and 2016, and 2) changes in the unadjusted prevalence ratio (PR) of comorbidities in HIV-positive versus HIV-negative admissions over time. Of 898,139 hospital admissions from 2006-2016, 19,039 (2.1%) were HIV-positive. Across all admissions during the study period, the greatest comorbidity disparities between HIV-positive and HIV-negative admissions were mild liver disease (PR=4.9, 95% CI: [4.8,5.1]), moderate or severe liver disease (PR=2.2 [2.0,2.4]), and chronic pulmonary disease (PR=1.8 [1.8,1.8]). The prevalence and relative burden of comorbidities among hospitalized PLHIV is changing over time. Careful monitoring and intensive discharge planning may be effective strategies for addressing the evolving health needs of PLHIV.

MeSH Terms

-

Keywords

HIV; aging with HIV; comorbidities

Frailty Significantly Associated with a Risk for Mid-term Outcomes in Elderly Chronic Coronary Syndrome Patients: a Prospective Study.

Abstract

Frailty is a condition of elderly characterized by increased vulnerability to stressful events. Frail patients are more likely to have adverse events. The purposes of this study were to define frailty in patients aged ≥ 70 years with chronic coronary syndrome (CCS) and to evaluate mortality and prognostic significance of frailty in these patients. We included 99 patients, ≥ 70 years old (mean age 74±5.3 years), with diagnosis of CCS. They were followed-up for up to 12 months. The frailty score was evaluated according to the Canadian Study of Health and Aging (CSHA). All patients were divided as frail or non-frail. The groups were compared for their characteristics and clinical outcomes. Fifty patients were classified as frail, and 49 patients as non-frail. The 12-month Major Adverse Cardiac Events (MACE) rate was 69.4% in frail patients and 20% in non-frail patients. Frailty increases the risk for MACE as much as 3.48 times. Two patients died in the non-frail group and 11 patients died in the frail group. Frailty increases the risk for death as much as 6.05 times. When we compared the aforementioned risk factors by multivariate analysis, higher CSHA frailty score was associated with increased MACE and death (relative risk [RR] = 22.94, 95% confidence interval [CI] 3.33-158.19, P=0.001, for MACE; RR = 7.41, 95% CI 1.44-38.03, P=0.016, for death). Being a frail elderly CCS patient is associated with worse outcomes. Therefore, frailty score should be evaluated for elderly CCS patients as a prognostic marker.

MeSH Terms

-

Keywords

Aging; Canada; Confidence Intervals; Death; Frail Elderly; Frailty; Heart; Multivariate Analysis; Prognosis; Risk Factors

Natural products targeting mitochondria: emerging therapeutics for age-associated neurological disorders.

Abstract

Mitochondria are the primary source of energy production in the brain thereby supporting most of its activity. However, mitochondria become inefficient and dysfunctional with age and to a greater extent in neurological disorders. Thus, mitochondria represent an emerging drug target for many age-associated neurological disorders. This review summarizes recent advances (covering from 2010 to May 2020) in the use of natural products from plant, animal, and microbial sources as potential neuroprotective agents to restore mitochondrial function. Natural products from diverse classes of chemical structures are discussed and organized according to their mechanism of action on mitochondria in terms of modulation of biogenesis, dynamics, bioenergetics, calcium homeostasis, and membrane potential, as well as inhibition of the oxytosis/ferroptosis pathway. This analysis emphasizes the significant value of natural products for mitochondrial pharmacology as well as the opportunities and challenges for the discovery and development of future neurotherapeutics.

MeSH Terms

-

Keywords

Natural products; aging; drug discovery; mitochondrial dysfunction; neurological disorders; neuropharmacology; oxytosis/ferroptosis

Forever young: the key to rejuvenation during gametogenesis.

Abstract

Cell aging is the result of deteriorating competence in maintaining cellular homeostasis and quality control. Certain cell types are able to rejuvenate through asymmetric cell division by excluding aging factors, including damaged cellular compartments and extrachromosomal rDNA circles, from entering the daughter cell. Recent findings from the budding yeast S. cerevisiae have shown that gametogenesis represents another type of cellular rejuvenation. Gametes, whether produced by an old or a young mother cell, are granted a renewed replicative lifespan through the formation of a fifth nuclear compartment that sequesters the harmful senescence factors accumulated by the mother. Here, we describe the importance and mechanism of cellular remodeling at the nuclear envelope mediated by ESCRT-III and the LEM-domain proteins, with a focus on nuclear pore biogenesis and chromatin interaction during gamete rejuvenation.

MeSH Terms

-

Keywords

ESCRT-III; LEM-domain; Meiosis; Nuclear pore complex; Replicative lifespan

Electronic Medication Management System Introduction and Deprescribing Practice in Post-Acute Care.

Abstract

To determine the effect of introducing an electronic medication management system (EMMS) on deprescribing practice in a post-acute hospital setting. This study used a before-after study design. This study examined the admission and discharge medications prescribed to patients admitted to an Australian post-acute hospital before and after the introduction of an EMMS. Data were collected over a 1-month period before and after the introduction of an EMMS and included summary measures of drug burden including Potentially Inappropriate Medications and the Drug Burden Index. We calculated and compared admission and discharge medication prescription as well as change in medication use before and after the introduction of an EMMS. Medication prescription data were available for 121 people before and 107 people after EMMS introduction. In both phases, when compared with admission, those discharged were prescribed fewer medications (mean reduction pre-EMMS = 2.9, P < .001, post-EMMS = 2.6, P < .001), fewer Potentially Inappropriate Medications (mean reduction pre-EMMS = 0.4, P < .001, post-EMMS = 0.6, P < .001) and had lower Drug Burden Index (mean reduction pre-EMMS = 0.1, P < .001, post-EMMS = 0.2, P < .001). The degree of reduction in each measure was similar before and after EMMS introduction. The introduction of an EMMS did not affect deprescribing practice in a post-acute hospital setting. Future work is required to explore the potential for clinical decision support within an EMMS to further improve the safety and effectiveness of deprescribing within post-acute care.

MeSH Terms

-

Keywords

Deprescribing; electronic prescribing; geriatrics; polypharmacy; potentially inappropriate medication

Are Positive Childhood Experiences Linked to Better Cognitive Functioning in Later Life?: Examining the Role of Life Course Pathways.

Abstract

We examine whether childhood family well-being is associated with cognitive functioning and to what extent the association between the family context and cognitive functioning is explained by adulthood resources.   Data are drawn from the National Social Life, Health, and Aging Project Wave 3 (2015/2016; [i]N[/i] = 3361). We measured cognitive functioning using the Montreal Cognitive Assessment. Childhood family factors included family-life happiness, family structure, and family socioeconomic status. Education, social connectedness, self-mastery, and self-rated health were assessed as adulthood resources.   Respondents who grew up in a happy family had significantly higher levels of cognitive functioning. The formal mediation test suggests that a happy family life during childhood has a positive association with later cognition, in part, by enhancing self-mastery in adulthood.   Our findings provide evidence that positive childhood experiences are linked to later life cognition. The sense of control people have over their life circumstances is one potential pathway explaining this association.

MeSH Terms

-

Keywords

National Social Life, Health and Aging Project; childhood happiness; cognitive function; cumulative advantage; self-mastery

Reduced pericyte and tight junction coverage in old diabetic rats are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction.

Abstract

Diabetes mellitus (DM) is one of the primary pathological factors that contributes to aging-related cognitive impairments, but the underlying mechanisms remain unclear. We recently reported that old DM rats exhibited impaired myogenic responses of the cerebral arteries and arterioles, poor cerebral blood flow autoregulation, enhanced blood-brain barrier (BBB) leakage, and cognitive impairments. These changes were associated with diminished vascular smooth muscle cell contractile capability linked to elevated reactive oxygen species (ROS) and reduced ATP production. The present study, using a non-obese T2DN DM rat, isolated parenchymal arterioles (PAs), and cultured cerebral microvascular pericytes, examined whether cerebrovascular pericyte in DM is damaged and whether pericyte dysfunction may play a role in the regulation of cerebral hemodynamics and BBB integrity. We found that ROS and mitochondrial superoxide production were elevated in PAs isolated from old DM rats and in high glucose (HG)-treated alpha-smooth muscle actin positive pericytes. HG-treated pericytes displayed decreased contractile capability in association with diminished mitochondrial respiration and ATP production. Additionally, the expression of advanced glycation end products, transforming growth factor-beta, vascular endothelial growth factor, and fibronectin were enhanced, but claudin 5 and integrin β1 was reduced in the brain of old DM rats and HG-treated pericytes. Further, endothelial tight junction and pericyte coverage on microvessels were reduced in the cortex of old DM rats. These results demonstrate our previous findings that the impaired cerebral hemodynamics and BBB leakage and cognitive impairments in the same old DM model are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction.

MeSH Terms

-

Keywords

Diabetes mellitus; aging; blood-brain barrier; cerebral vascular pericytes; oxidative stress

Age range implications of rats over Strongyloides venezuelensis infection.

Abstract

To evaluate the dynamics of S. venezuelensis infection in Wistar rats of different age ranges. Thirty-five (n = 35, 7 per group) male Wistar rats were distributed according to age into five groups: 2, 3, 6, 12 and 18 months old (mo). The rats were infected by S. venezuelensis and eggs per gram of feces (EPG) were measured at 3, 9, 15 and 21 days post-infection (dpi). All animals were killed at 21 dpi, thymus, lungs and small intestines were removed, and relative weight calculated. The adult worms recovered from the small intestines and blood cells were counted. Rats in advanced age presented higher parasite oviposition at 9 dpi and posterior reduction of EPG, while young rats still showed higher oviposition at 15 dpi and 21 dpi. At 12 and 18 mo, the rats had greater number of adult worms, which with low fecundity, eosinophilia and least concentration of monocytes. The fecundity of worms was more expressive in young rats. A strong correlation was observed between age and EPG at 9 dpi (R = 0.72, p < 0.0001), at 15 (R = -0.66, p < 0.0001) and at 21 dpi (R = -0.65, p < 0.0001), as well as age and numbers of worms at 21 dpi (R = 0.74, p < 0.0001). The relative weight of the thymus, lungs and small intestines were higher in rats at 2 and 3 mo in comparison to the older groups of rats. Aging process interfered on host-parasite relationship and changed the dynamics of infection of S. venezuelensis in Wistar rats.

MeSH Terms

-

Keywords

Aging; Parasitic disease; Strongyloidiasis

Issues Associated With the Management and Governance of Sensor Data and Information to Assist Aging in Place: Focus Group Study With Health Care Professionals.

Abstract

Smart home and telemonitoring technologies have often been suggested to assist health care workers in supporting older people to age in place. However, there is limited research examining diverse information needs of different groups of health care workers and their access to appropriate information technologies. The aim of this study was to investigate the issues associated with using technologies that connect older people to their health care providers to support aging in place and enhance older people's health and well-being. Seven focus group discussions were conducted comprising 44 health care professionals who provided clinic-based or in-home services to community-dwelling older people. Participants were asked about their information needs and how technology could help them support older people to age in place. The recordings of the sessions were transcribed and thematically analyzed. The perspectives varied between the respondents who worked in primary care clinics and those who worked in community-based services. Three overarching themes were identified. The first theme was "access to technology and systems," which examined the different levels of technology in use and the problems that various groups of health care professionals had in accessing information about their patients. Primary care professionals had access to good internal information systems but they experienced poor integration with other health care providers. The community-based teams had poor access to technology. The second theme was "collecting and sharing of information," which focused on how technology might be used to provide them with more information about their patients. Primary care teams were interested in telemonitoring for specific clinical indicators but they wanted the information to be preprocessed. Community-based teams were more concerned about gaining information on the patients' social environment. The third theme was that all respondents identified similar "barriers to uptake": cost and funding issues, usability of systems by older people, and information security and privacy concerns. The participants perceived the potential benefits of technologies, but they were concerned that the information they received should be preprocessed and integrated with current information systems and tailored to the older people's unique and changing situations. Several management and governance issues were identified, which needed to be resolved to enable the widespread integration of these technologies into the health care system. The disconnected nature of the current information architecture means that there is no clear way for sensor data from telemonitoring and smart home devices to be integrated with other patient information. Furthermore, cost, privacy, security, and usability barriers also need to be resolved. This study highlights the importance and the complexity of management and governance of systems to collect and disseminate such information. Further research into the requirements of all stakeholder groups and how the information can be processed and disseminated is required.

MeSH Terms

-

Keywords

aging; aging in place; elderly health; home monitoring technology; information governance; information management; older people; smart home; support network

IL-1β-MyD88-mTOR Axis Promotes Immune-Protective IL-17A Foxp3 Cells During Mucosal Infection and Is Dysregulated With Aging.

Abstract

CD4 Foxp3 T maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3 cells altered their function and resulted in increased fungal burden and immunopathology during oral [i]Candida albicans[/i] (CA) challenge. Excessive inflammation due to the absence of MyD88 in T coincided with a reduction of the unique population of IL-17A expressing Foxp3 cells (T 17) and an increase in dysfunctional IFN-γ /Foxp3 cells (T IFN-γ) in infected mice. Failure of MyD88 T to regulate effector CD4 T cell functions correlated with heightened levels of IFN-γ in CD4 T cells, as well as increased infiltration of inflammatory monocytes and neutrophils in oral mucosa [i]in vivo[/i]. Mechanistically, IL-1β/MyD88 signaling was required for the activation of IRAK-4, Akt, and mTOR, which led to the induction and proliferation of T 17 cells. In the absence of IL-1 receptor signaling, T 17 cells were reduced, but IL-6-driven expansion of T IFN-γ cells was increased. This mechanism was physiologically relevant during [i]Candida[/i] infection in aged mice, as they exhibited IL-1 receptor/MyD88 defect in Foxp3 cells, loss of p-mTOR T 17 cells and reduced levels of IL-1β in oral mucosa, which coincided with persistent tongue inflammation. Concurrent with T dysfunction, aging was associated with increased CD4 T cell hyperactivation and heightened levels of IL-6 in mice and humans in oral mucosa [i]in vivo[/i]. Taken together, our data identify IL-1β/MyD88/T axis as a new component that modulates inflammatory responses in oral mucosa. Also, dysregulation of this axis in an aging immune system may skew host defense towards an immunopathological response in mucosal compartments.

MeSH Terms

-

Keywords

Candida; Foxp3; IL-1β; Treg; Treg17; aging; fungal infection; senescence

High-resolution mouse subventricular zone stem-cell niche transcriptome reveals features of lineage, anatomy, and aging.

Abstract

Adult neural stem cells (NSC) serve as a reservoir for brain plasticity and origin for certain gliomas. Lineage tracing and genomic approaches have portrayed complex underlying heterogeneity within the major anatomical location for NSC, the subventricular zone (SVZ). To gain a comprehensive profile of NSC heterogeneity, we utilized a well-validated stem/progenitor-specific reporter transgene in concert with single-cell RNA sequencing to achieve unbiased analysis of SVZ cells from infancy to advanced age. The magnitude and high specificity of the resulting transcriptional datasets allow precise identification of the varied cell types embedded in the SVZ including specialized parenchymal cells (neurons, glia, microglia) and noncentral nervous system cells (endothelial, immune). Initial mining of the data delineates four quiescent NSC and three progenitor-cell subpopulations formed in a linear progression. Further evidence indicates that distinct stem and progenitor populations reside in different regions of the SVZ. As stem/progenitor populations progress from neonatal to advanced age, they acquire a deficiency in transition from quiescence to proliferation. Further data mining identifies stage-specific biological processes, transcription factor networks, and cell-surface markers for investigation of cellular identities, lineage relationships, and key regulatory pathways in adult NSC maintenance and neurogenesis.

MeSH Terms

-

Keywords

aging; neural stem cell; single-cell RNA sequencing; subventricular zone; transcriptome

MYSM1 Suppresses Cellular Senescence and the Aging Process to Prolong Lifespan.

Abstract

Aging is a universal feature of life that is a major focus of scientific research and a risk factor in many diseases. A comprehensive understanding of the cellular and molecular mechanisms of aging are critical to the prevention of diseases associated with the aging process. Here, it is shown that MYSM1 is a key suppressor of aging and aging-related pathologies. MYSM1 functionally represses cellular senescence and the aging process in human and mice primary cells and in mice organs. MYSM1 mechanistically attenuates the aging process by promoting DNA repair processes. Remarkably, MYSM1 deficiency facilitates the aging process and reduces lifespan, whereas MYSM1 over-expression attenuates the aging process and increases lifespan in mice. The functional role of MYSM1 is demonstrated in suppressing the aging process and prolonging lifespan. MYSM1 is a key suppressor of aging and may act as a potential agent for the prevention of aging and aging-associated diseases.

MeSH Terms

-

Keywords

DNA repair; Myb‐like, SWIRM, and MPN domains‐containing protein 1 (MYSM1); aging; senescence; senescence‐associated secretory phenotype (SASP)

A Single-Cell Transcriptomic Atlas of Human Skin Aging.

Abstract

Skin undergoes constant self-renewal, and its functional decline is a visible consequence of aging. Understanding human skin aging requires in-depth knowledge of the molecular and functional properties of various skin cell types. We performed single-cell RNA sequencing of human eyelid skin from healthy individuals across different ages and identified eleven canonical cell types, as well as six subpopulations of basal cells. Further analysis revealed progressive accumulation of photoaging-related changes and increased chronic inflammation with age. Transcriptional factors involved in the developmental process underwent early-onset decline during aging. Furthermore, inhibition of key transcription factors HES1 in fibroblasts and KLF6 in keratinocytes not only compromised cell proliferation, but also increased inflammation and cellular senescence during aging. Lastly, we found that genetic activation of HES1 or pharmacological treatment with quercetin alleviated cellular senescence of dermal fibroblasts. These findings provide a single-cell molecular framework of human skin aging, providing a rich resource for developing therapeutic strategies against aging-related skin disorders.

MeSH Terms

-

Keywords

HES1; KLF6; aging; fibroblast; keratinocyte; quercetin; senescence; single-cell RNA sequencing; skin

Senescence in Pulmonary Fibrosis: Between Aging and Exposure.

Abstract

To date, chronic pulmonary pathologies represent the third leading cause of death in the elderly population. Evidence-based projections suggest that >65 (years old) individuals will account for approximately a quarter of the world population before the turn of the century. Genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication, are described as the nine "hallmarks" that govern cellular fitness. Any deviation from the normal pattern initiates a complex cascade of events culminating to a disease state. This blueprint, originally employed to describe aberrant changes in cancer cells, can be also used to describe aging and fibrosis. Pulmonary fibrosis (PF) is the result of a progressive decline in injury resolution processes stemming from endogenous (physiological decline or somatic mutations) or exogenous stress. Environmental, dietary or occupational exposure accelerates the pathogenesis of a senescent phenotype based on (1) window of exposure; (2) dose, duration, recurrence; and (3) cells type being targeted. As the lung ages, the threshold to generate an irreversibly senescent phenotype is lowered. However, we do not have sufficient knowledge to make accurate predictions. In this review, we provide an assessment of the literature that interrogates lung epithelial, mesenchymal, and immune senescence at the intersection of aging, environmental exposure and pulmonary fibrosis.

MeSH Terms

-

Keywords

aging; epithelial cells; immune-senescence; inflamm-aging; lung fibrosis; mesenchymal senescence; senescence

GERO Cohort Protocol, Chile, 2017-2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly.

Abstract

With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research. The GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being. Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research. NCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.

MeSH Terms

-

Keywords

Alzheimer; Cognitive aging; Dementia; Functional decline; Geroscience; Subjective cognitive complaint

Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination.

Abstract

Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function. Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure antibody titers, due to a previous infection or vaccination, have less probability to get infected. Examples of this exception are the elderly individuals infected during the 2009 pandemic season who made antibodies with broader epitope recognition and higher avidity than those made by younger individuals. Several studies have allowed the identification of B cell intrinsic defects accounting for sub-optimal antibody responses of elderly individuals. These defects include 1) reduced class switch recombination, responsible for the generation of a secondary response of class switched antibodies, 2) reduced de novo somatic hypermutation of the antibody variable region, 3) reduced binding and neutralization capacity, as well as binding specificity, of the secreted antibodies, 4) increased epigenetic modifications that are associated with lower antibody responses, 5) increased frequencies of inflammatory B cell subsets, and 6) shorter telomeres. Although influenza vaccination represents the most effective way to prevent influenza infection, vaccines with greater immunogenicity are needed to improve the response of elderly individuals. Recent advances in technology have made possible a broad approach to better understand the age-associated changes in immune cells, needed to design tailored vaccines and effective therapeutic strategies that will be able to improve the immune response of vulnerable individuals.

MeSH Terms

-

Keywords

Aging; Antibodies; B cells; Influenza infection; Influenza vaccination

The regulatory framework of developmentally programmed cell death in floral organs: A review.

Abstract

Developmentally programmed cell death (dPCD) is a tightly controlled biological process. In recent years, vital roles of dPCD on regulating floral organ growth and development have been reported. It is well known that flower is an essential organ for reproduction and a turning point of plants' life cycle. Hence, uncovering the complex molecular networks which regulates dPCD processes in floral organs is utmost important. So far, our understanding of dPCD on floral organ growth and development is just starting. Herein, we summarize the important factors that involved in the tapetal degeneration, pollen tube rupture, receptive synergid cell death, nucellar degradation, and antipodal cell degradation. Meanwhile, the known factors that involved in transmitting tract formation and self-incompatibility-induced PCD were also introduced. Furthermore, the genes that associated with anther dehiscence and petal senescence and abscission were reviewed as well. The functions of various types of factors involved in floral dPCD processes are highlighted principally. The regulatory panorama described here can provide us some insights about flower-specific dPCD process.

MeSH Terms

-

Keywords

Floral organ; Programmed cell death; Regulatory network; Senescence; Transcriptional factor

Positivity in Younger and in Older Age: Associations With Future Time Perspective and Socioemotional Functioning.

Abstract

Aging has been associated with a motivational shift to positive over negative information (i.e., positivity effect), which is often explained by a limited future time perspective (FTP) within the framework of socioemotional selectivity theory (SST). However, whether a limited FTP functions similarly in younger and older adults, and whether inter-individual differences in socioemotional functioning are similarly associated with preference for positive information (i.e., positivity) is still not clear. We investigated younger (20-35 years, [i]N[/i] = 73) and older (60-75 years, [i]N[/i] = 56) adults' gaze preferences on pairs of happy, angry, sad, and neutral faces using an eye-tracking system. We additionally assessed several parameters potentially underlying inter-individual differences in emotion processing such as FTP, stress, cognitive functioning, social support, emotion regulation, and well-being. While we found no age-related differences in positivity when the entire trial duration was considered, older adults showed longer fixations on the more positive face in later stages of processing (i.e., [i]positivity shifts[/i]). This allocation of resources toward more positive stimuli might serve an emotion regulatory purpose and seems consistent with the SST. However, our findings suggest that age moderates the relationship between FTP and positivity shifts, such that the relationship between FTP and positivity preferences was negative in older, and positive in younger adults, potentially stemming from an age-related differential meaning of the FTP construct across age. Furthermore, our exploratory analyses showed that along with the age and FTP interaction, lower levels of worry also played a significant role in positivity shifts. We conclude that positivity effects cannot be solely explained by aging, or the associated reduced FTP [i]per se[/i], but is rather determined by a complex interplay of psychosocial and emotional features.

MeSH Terms

-

Keywords

aging; future time perspective; positivity bias; positivity effect; socioemotional functioning; socioemotional selectivity theory; well-being; worry

Cancer Risk in the Heart Failure Population: Epidemiology, Mechanisms, and Clinical Implications.

Abstract

Along with population aging, the incidence of both heart failure (HF) and cancer is increasing. However, little is known about new-onset cancer in HF patients. This review aims at showing recent discoveries concerning this subset of patients. Not only cancer and HF share similar risk factors but also HF itself can stimulate cancer development. Some cytokines produced by the failing heart induce mild inflammation promoting carcinogenesis, as it has been recently suggested by an experimental model of HF in mice. The incidence of new-onset cancer is higher in HF patients compared to the general population, and it significantly worsens their prognosis. Moreover, the management of HF patients developing new-onset cancer is challenging, especially due to the limited therapeutic options for patients affected by both cancer and HF and the higher risk of cardiotoxicity from anticancer drugs.

MeSH Terms

-

Keywords

Aging; Cancer; Cardio-oncology; Heart failure; Pathophysiology; Risk factors

A Dynamic Anomaly Detection Approach Based on Permutation Entropy for Predicting Aging-Related Failures.

Abstract

Software aging is a phenomenon referring to the performance degradation of a long-running software system. This phenomenon is an accumulative process during execution, which will gradually lead the system from a normal state to a failure-prone state. It is a crucial challenge for system reliability to predict the Aging-Related Failures (ARFs) accurately. In this paper, permutation entropy (PE) is modified to Multidimensional Multi-scale Permutation Entropy (MMPE) as a novel aging indicator to detect performance anomalies, since MMPE is sensitive to dynamic state changes. An experiment is set on the distributed database system Voldemort, and MMPE is calculated based on the collected performance metrics during execution. Finally, based on MMPE, a failure prediction model using the machine learning method to reveal the anomalies is presented, which can predict failures with high accuracy.

MeSH Terms

-

Keywords

anomaly detection; failure prediction; machine learning; software aging

Acoustic pre-stimulation modulates startle and postural reactions during sudden release of standing support surface in aging.

Abstract

Falls contribute to injuries and reduced level of physical activity in older adults. During falls, the abrupt sensation of moving downward triggers a startle-like reaction that may interfere with protective response movements necessary to maintain balance. Startle reaction could be dampened by sensory pre-stimulation delivered immediately before a startling stimulus. This study investigated the neuromodulatory effects of pre-stimulation on postural/startle responses to drop perturbations of the standing support surface in relation to age. Ten younger and 10 older adults stood quietly on an elevated computer-controlled moveable platform. At an unpredictable time, participants were dropped vertically to elicit a startle-like response. Reactive drop perturbation trials without a pre-stimulus (control) were alternated with trials with acoustic pre-stimulus tone (PSI). A two-way mixed design analysis of variance comparing condition (control vs. PSI) X group (younger vs. older) was performed to analyze changes in muscle activation patterns, ground reaction force, and joint angular displacements. Compared to younger adults, older adults showed lower neck muscle electromyography amplitude reduction rate and incidence of response. Peak muscle activation in neck, upper arm, and hamstring muscles were reduced during PSI trials compared to control trials in both groups (p < 0.05). In addition, knee and hip joint flexion prior to ground contact was reduced in PSI trials compared to control (p < 0.05). During post-landing balance recovery, increased knee and hip flexion displacement and time to peak impact force were observed in PSI trials compared to control condition (p < 0.05). PSI reduced startle-induced muscle activation at proximal body segments and likely decreased joint flexion during abrupt downward vertical displacement perturbations of the body. Older adults retained the ability to modulate startle and postural responses but their neuromodulatory capacity was reduced compared with younger adults. Further research on the potential of applying PSI as a possible therapeutic tool to reduce the risk of fall-related injury is needed.

MeSH Terms

-

Keywords

Aging; Falls; Pre-stimulus inhibition; Startle

[Consensus and controversy on imaging of aging-related cerebral small vessel disease].

Abstract

---

MeSH Terms

Aging

• Brain
• Cerebral Small Vessel Diseases
• Consensus
• Humans
• Magnetic Resonance Imaging

Keywords

-

Human variation in response to food and nutrients.

Abstract

The application of science to human nutrition over the centuries has served societies well. One example is the identification of key nutrients to overcome nutritional deficiencies, which has enhanced life expectancy. Enhanced life expectancy, however, is associated with an increased prevalence of chronic disorders related to food and nutrition. Findings of studies indicating that individual responses to nutrients differ substantially between individuals make it necessary to re-examine the relationship between nutrition and human health. The emergence of new genomic-based technologies illustrates the complexity and scale of the interactions between nutrition and genetic factors. Epigenetic modifications resulting from interactions of the genetic profile, aging, and lifestyle can influence the time course of chronic disorders and contribute to human variability in response to nutritional interventions. Developing a better understanding of human variability as it applies to human nutrition will involve embracing the approaches and principles of complex science.

MeSH Terms

-

Keywords

chronic diseases; complex science; epigenetics; genome; human variability; longevity; nutrition; personalized nutrition

Sustainability of residential environmental interventions and health outcomes in the elderly.

Abstract

Research has documented that housing conditions can negatively impact the health of residents. Asthma has many known indoor environmental triggers including dust, pests, smoke and mold, as evidenced by the 25 million people in the U.S. population who have asthma. The paper describes a follow-up study involving elder adults with asthma who participated in a multifaceted home educational and environmental intervention shown to produce significant health benefits. On average the time between the end of the prior intervention study and the follow-up was 2.3 years. The objective of this study was to evaluate whether improvements in environmental conditions and health outcomes resulting from the original Older Adult Study (OAS, multifaceted educational and environmental interventions) would be maintained or decline over time for these low income seniors with asthma. Health assessment included data on respiratory health outcomes included the Saint George's Respiratory Questionnaire (SGRQ) and Asthma Control Test from the original Older Adult Study (OAS) and this follow-up Older Adult Study (OAFS) along with health care utilization data. Environmental assessments included evaluation of asthma trigger activities (ATAs) and exposures before and after the original healthy homes intervention (questionnaire, home survey) and at this follow-up. Assessments were conducted in English, Khmer and Spanish. At assessment in the Older Adult Follow-up Study (OAFS), the older adults maintained some of the health improvements gained during the OAS when compared to the OAS pre-intervention baseline. However, health outcomes declined from the OAS final assessment to the OAFS (only the SGRQ Impact scores were significantly different). These findings suggest that further study with a larger population is needed to determine if the significant health outcome improvements from multifaceted home educational and environmental interventions (OAS) could be more strongly maintained by providing additional follow-up "booster" interventions to this older adult population with asthma.

MeSH Terms

-

Keywords

Aging in place; Asthma; Environmental health; Healthy housing

Attendant's experience with the personalized citizen assistance for social participation (APIC).

Abstract

To promote healthy aging, the social participation needs of older adults must be better met. Previous studies have shown the benefits of the Personalized citizen assistance for social participation (APIC), but few explored its influence on attendants. This study explored the assistance experience of attendants in providing the APIC to older adults with disabilities. A qualitative design inspired by a phenomenological approach was used with six female attendants who participated in individual interviews. The APIC attendants felt useful, developed meaningful relationships with their older adults, and improved their self-knowledge. Attendants had the opportunity to reflect on their lives and self-aging. They contributed to older adults' functional independence, motivation, and participation in social activities. Attendants encountered challenges related to withdrawn behavior in older adults, such as refusing to participate in activities. Considering the identified benefits of the APIC for attendants, further studies should explore personalized assistance to preserve older adults' health.

MeSH Terms

-

Keywords

Aging; Community integration; Community participation; Health promotion; Individualized assistance

Senescent cell accumulation mechanisms inferred from parabiosis.

Abstract

Senescent cells are growth-arrested cells that cause inflammation and play a causal role in aging. They accumulate with age, and preventing this accumulation delays age-related diseases. However, the mechanism for senescent cell accumulation is not fully understood. Accumulation can result from increasing production or decreasing removal of senescent cells with age, or both. To distinguish between these possibilities, we analyze data from parabiosis, the surgical conjoining of two mice so that they share circulation. Parabiosis between a young and old mouse, called heterochronic parabiosis, reduces senescent cell levels in the old mouse, while raising senescent cell levels in the young mouse. We show that parabiosis data can reject mechanisms for senescent cell accumulation in which only production rises with age or only removal decreases with age; both must vary with age. Since removal drops with age, senescent cell half-life rises with age. This matches a recent model for senescent cell accumulation developed from independent data on senescent cell dynamics, called the SR model, in which production rises linearly with age and senescent cells inhibit their own removal. The SR model further explains the timescales and mechanism of rejuvenation in parabiosis, based on transfer of spare removal capacity from the young mouse to the old. The present quantitative understanding can help design optimal treatments that remove senescent cells, by matching the time between treatments to the time it takes senescent cells to re-accumulate.

MeSH Terms

-

Keywords

Aging; Mathematical modeling; Parabiosis; Senescent cells; Systems biology

Epigenetic Clock Analysis in Children with Fetal Alcohol Spectrum Disorder.

Abstract

Fetal alcohol spectrum disorder (FASD) is characterized by severe clinical impairment, considerable social burden, and high mortality and morbidity, which are due to various malformations, sepsis, and cancer. As > 50% of deaths from FASD occur during the first year of life, we hypothesized that there is the acceleration of biological aging in FASD. Several recent studies have established genome-wide DNA methylation (DNAm) profiles as "epigenetic clocks" that can estimate biological aging, and FASD has been associated with differential DNAm patterns. Therefore, we tested this hypothesis using epigenetic clocks. We investigated five DNAm-based measures of epigenetic age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and telomere length (DNAmTL) using four independent publicly available DNAm datasets; two datasets were derived from buccal epithelium, and the other two datasets were derived from peripheral blood. Compared to controls, children with FASD exhibited an acceleration of GrimAge in one buccal and two blood datasets. No significant difference was found in other DNAm ages and DNAmTL. Meta-analyses showed a significant acceleration of GrimAge in the blood samples but not in the buccal samples. This study provides novel evidence regarding accelerated epigenetic aging in children with FASD.

MeSH Terms

-

Keywords

Biological Aging; DNA Methylation; Epigenetic Clock; Fetal Alcohol Spectrum Disorder; Prenatal Alcohol Use

Microstructural differences in white matter tracts across middle to late adulthood: a diffusion MRI study on 7167 UK Biobank participants.

Abstract

White matter fiber tracts demonstrate heterogeneous vulnerabilities to aging effects. Here, we estimated age-related differences in tract properties using UK Biobank diffusion magnetic resonance imaging data of 7167 47- to 76-year-old neurologically healthy people (3368 men and 3799 women). Tract properties in terms of generalized fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were sampled on 76 fiber tracts; for each tract, age-related differences were estimated by fitting these indices against age in a linear model. This cross-sectional study demonstrated 4 age-difference patterns. The dominant pattern was lower generalized fractional anisotropy and higher axial diffusivity, radial diffusivity, and mean diffusivity with age, constituting 45 of 76 tracts, mostly involving the association, projection, and commissure fibers connecting the prefrontal lobe. The other 3 patterns constituted only 14 tracts, with atypical age differences in diffusion indices, and mainly involved parietal, occipital, and temporal cortices. By analyzing the large volume of diffusion magnetic resonance imaging data available from the UK Biobank, the study has provided a detailed description of heterogeneous age-related differences in tract properties over the whole brain which generally supports the myelodegeneration hypothesis.

MeSH Terms

-

Keywords

Brain aging; Diffusion MRI; Fiber degeneration; Magnetic resonance imaging; UK Biobank; White matter

Targeting Senescent Cells for a Healthier Aging: Challenges and Opportunities.

Abstract

Aging is a physiological decline in both structural homeostasis and functional integrity, progressively affecting organismal health. A major hallmark of aging is the accumulation of senescent cells, which have entered a state of irreversible cell cycle arrest after experiencing inherent or environmental stresses. Although cellular senescence is essential in several physiological events, it plays a detrimental role in a large array of age-related pathologies. Recent biomedical advances in specifically targeting senescent cells to improve healthy aging, or alternatively, postpone natural aging and age-related diseases, a strategy termed senotherapy, have attracted substantial interest in both scientific and medical communities. Challenges for aging research are highlighted and potential avenues that can be leveraged for therapeutic interventions to control aging and age-related disorders in the current era of precision medicine.

MeSH Terms

-

Keywords

aging; clinical trials; healthspan; senescent cells; senolytics; senotherapy

HCAR Is a Limitation Factor for Chlorophyll Cycle and Chlorophyll [i]b[/i] Degradation in Chlorophyll-[i]b[/i]-Overproducing Plants.

Abstract

The chlorophyll (Chl) cycle is the metabolic pathway for Chl [i]a[/i] and Chl [i]b[/i] inter-conversion. In this pathway, Chl [i]b[/i] is synthesized from Chl [i]a[/i] by the catalyzing action of chlorophyllide [i]a[/i] oxygenase (CAO). In contrast, Chl [i]b[/i] is firstly reduced to produce 7-hydroxymethyl Chl (HMChl) [i]a[/i], which is catalyzed by two isozymes of Chl [i]b[/i] reductase (CBR), non-yellow coloring 1 (NYC1) and NYC1-like (NOL). Subsequently, HMChl [i]a[/i] is reduced to Chl [i]a[/i] by HMChl [i]a[/i] reductase (HCAR). CAO plays a pivotal role in Chl [i]a[/i]/[i]b[/i] ratio regulation and plants over-accumulate Chl [i]b[/i] in CAO-overexpressing plants. NYC1 is more accumulated in Chl-[i]b[/i]-overproducing plants, while HCAR is not changed. To investigate the role of HCAR in Chl cycle regulation, the Chl metabolites of Chl-[i]b[/i]-overproducing plants were analyzed. The results showed that HMChl [i]a[/i] accumulated in these plants, and it decreased and the Chl [i]a[/i]/[i]b[/i] ratio increased by overexpressing HCAR, implying HCAR is insufficient for Chl cycle in Chl-[i]b[/i]-overproducing plants. Furthermore, during dark-induced senescence, the non-programmed cell death symptoms (leaves dehydrated with green color retained) of Chl-[i]b[/i]-overproducing plants were obviously alleviated, and the content of HM pheophorbide (HMPheide) [i]a[/i] and Pheide [i]b[/i] were sharply decreased by overexpressing HCAR. These results imply that HCAR is also insufficient for Chl degradation in Chl-[i]b[/i]-overproducing plants during senescence, thus causing the accumulation of Chl metabolites and non-programmed cell death of leaves. With these results taken together, we conclude that HCAR is not well regulated and it is a limiting factor for Chl cycle and Chl [i]b[/i] degradation in Chl-[i]b[/i]-overproducing plants.

MeSH Terms

-

Keywords

HCAR; cell death; chlorophyll cycle; chlorophyll degradation; leaf senescence

Disease- and Treatment-related Complications in Older Patients With Inflammatory Bowel Diseases: Comparison of Adult-onset vs Elderly-onset Disease.

Abstract

The incidence and prevalence of inflammatory bowel diseases (IBD) in older adults are rising. There is a limited comparative assessment of risk of disease- and treatment-related complications in older patients (older than 60 years) with adult-onset (age at disease onset, 18-59 years; AO-IBD) vs elderly-onset IBD (age at disease onset, older than 60 years; EO-IBD). We compared clinical outcomes in older patients with IBD with AO-IBD vs EO-IBD. We conducted a retrospective cohort study comparing risk of disease-related complications (IBD-related surgery, hospitalization, treatment escalation, clinical flare, or disease complication) and treatment-related complications (serious infection, malignancy, or death) in older patients with AO-IBD vs EO-IBD through Cox proportional hazard analysis, adjusting for age at cohort entry, disease phenotype, disease duration, prior surgery and/or hospitalization, medication use, disease activity at cohort entry, and comorbidities. We included 356 older patients with IBD (AO-IBD, 191 patients, 67 ± 5 y at cohort entry; EO-IBD, 165 patients, 72 ± 8 y at cohort entry). No significant differences were observed in the risk of disease-related complications in older patients with prevalent vs incident IBD (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.58-1.25), although risk of IBD-related surgery was lower in older patients with prevalent IBD (aHR, 0.47; 95% CI, 0.25-0.89). Older patients with prevalent IBD were significantly less likely to experience treatment-related complications (aHR, 0.58; 95% CI, 0.39-0.87). Patients with AO-IBD have lower risk of treatment-related complications as they age compared with patients with EO-IBD, without a significant difference in risk of disease-related complications.

MeSH Terms

-

Keywords

Crohn’s disease; aging; biologics; colitis; infections

Alleviation of tributyltin-induced toxicity by diet and microplastics in the marine rotifer Brachionus koreanus.

Abstract

To determine the effects of tributyltin (TBT) upon multiple exposures of diet and microplastic in rotifer, in vivo life parameters were measured. In 10 μg/L TBT-exposed rotifer, the 1 and 0.5 x diet groups resulted in reproduction reduction. However, 10 x diet treatment showed no significant changes in the total fecundity, despite a decrease in daily reproduction. Besides, differences in the lifespan were observed in response to different diet regimens. TBT and/or MP-exposed parental rotifer (F0) showed a significant delay in the pre-reproductive day under 0.5 x diet regimen. In all dietary regimens, exposure to TBT and MP induced an increase in reactive oxygen species, but antioxidant activities were perturbed. To further verify the carryover effect of TBT toxicity, progeny rotifer (F1) obtained from 24 h TBT and/or MP-exposed F0 was used. Interestingly, the faster hatching rate was observed only in F1 obtained from 1 x diet regimen-exposed F0. However, in the 0.5 x diet, the total fecundity was reduced and the pattern of the daily reproduction was collapsed. Thus, the toxicity of TBT can be alleviated by MP and nutrition status, but TBT-induced toxicity and its carryover effect are inevitable.

MeSH Terms

-

Keywords

Acute toxicity; Chronic toxicity; Lifespan; Maternal effect; Reproduction

On nitrogen fixation and "residual nitrogen content" in cellulosic pulps.

Abstract

Cellulosic material is capable of permanently retaining nitrogen compounds (mostly having amino functions), which is reflected in a residual nitrogen content (in the low per mille range to the low percent range) of some pulps and certain lab samples. Merely adsorptively bound compounds can be removed by mild acidic washing, but part of the nitrogen seems to be resistant and very tightly bound, and thus not accessible for removal by washing. Tertiary and aromatic amines are not retained in this way, but only primary and secondary amines. There is only a weak correlation between the "firmly bound nitrogen" and the carbonyl content in cellulosics (because of oxidative damage), so that possible aminal, Schiff base and enamine structures can hardly be relevant as major nitrogen sources. However, there is a very good linear correlation between the ISO brightness (chromophore content) in aged pulps and the residual nitrogen content. In particular the concentration of the cellulosic key chromophore 2,5-dihydroxy-[1,4]-benzoquinone (DHBQ) determines the permanent N-binding capacity of the pulp. DHBQ reacts very readily with primary and secondary amines under ambient conditions to 2,5-diamino-substituted [1,4]-benzoquinones, which have very low solubility (because of zwitterionic resonance contributions) and thus remain on/in the pulp. Examples of nitrogen fixation in pulps are the binding of piperidine (a common amine catalyst in derivatization reactions), amine degradation products of the cellulose solvent NMMO, dimethylamine in materials processed from the cellulose solvent DMAc/LiCl, imidazole (a degradation product of 1-alkyl-3-methylimidazolium ionic liquids), and of amino groups in proteins after enzymatic treatment. The nature of the respective DHBQ-amine addition compound has been verified by complete structure determination.

MeSH Terms

-

Keywords

Aging; Cellulose; Chromophores; Nitrogen fixation; Pulp; Residual nitrogen; Yellowing

Corrigendum: The Aging Slopes of Brain Structures Vary by Ethnicity and Sex: Evidence From a Large Magnetic Resonance Imaging Dataset From a Single Scanner of Cognitively Healthy Elderly People in Korea.

Abstract

[This corrects the article DOI: 10.3389/fnagi.2020.00233.].

MeSH Terms

-

Keywords

aging slope; ethnic difference; norm; normal aging; sex difference

Pharmacological blockade of TNFα prevents sarcopenia and prolongs survival in aging mice.

Abstract

Sarcopenia is a hallmark of aging. Inflammation due to increased generation of cytokines such as TNFα, IL-1β and IL-6 has been implicated in the pathogenesis of sarcopenia. In skeletal muscle of C57BL/6 mice from 12 until 28 months of age, we observed a progressive reduction of myofiber cross sectional area, loss of type II fibers and infiltration by inflammatory cells. Muscle strength decreased in parallel. Pharmacological TNFα blockade by weekly subcutaneous injection of Etanercept from 16 to 28 months of age prevented atrophy and loss of type II fibers, with significant improvements in muscle function and mice lifespan. The effects on leukocyte recruitment were limited. These results provide a proof of principle that endogenous TNFα is sufficient to cause sarcopenia and to reduce animal survival, and open a novel perspective on novel potential pharmacological treatment strategies based on TNFα blockade to prevent the noxious events associated with aging.

MeSH Terms

-

Keywords

TNF alpha; aging; inflammation; pharmacological intervention; sarcopenia

Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults.

Abstract

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA ) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope ( Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.

MeSH Terms

-

Keywords

autophagy; iron dyshomeostasis; iron isotopes; iron metabolism; mitochondria; mitochondrial quality control; mitophagy; muscle aging; oxidative stress; physical performance

City government's adoption of housing adaptation policy innovation for older adults: Evidence from China.

Abstract

Utilizing policy innovation and diffusion theory, this study aims to explain why city governments adopt housing adaptation policies that primarily benefit older people based on the case of China. The data are drawn from an event history dataset of a housing adaptation policy for older people collected from 283 Chinese cities from 2010 to 2018. Piecewise constant exponential models are utilized. The results indicate that cities facing greater internal pressure and a higher political status are more likely to adopt a housing adaptation policy for older people. Policy adoption by neighboring cities could further facilitate this process. Policy innovation and diffusion theory provides a useful framework for this study. That is, the Chinese city government's adoption of housing adaptation policy for older adults is initially driven by local needs and then accelerated by interactions among neighboring governments.

MeSH Terms

-

Keywords

Aging in place; Housing accessibility; Piecewise constant exponential model; Policy innovation

Higher Impact Physical Activity is Associated with Maintenance of Bone Mineral Density but Not Reduced Incident Falls or Fractures in Older Men: The Concord Health and Ageing in Men Project.

Abstract

High-impact physical activities with bone strains of high magnitude and frequency may benefit bone health. This study aimed to investigate the longitudinal associations between changes in loading intensities and application rates, estimated from self-reported physical activity, with bone mineral density (BMD) changes over five years, and also with incident falls over two years and long-term incident fractures, in community-dwelling older men. 1,599 men (mean age 76.8±5.4 years) from the Concord Health and Ageing in Men Project (CHAMP) were assessed at baseline (2005-2007), 2-year and 5-year follow-up. At each time point, hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and physical activity energy expenditure over the past week was self-reported via the Physical Activity Scale for the Elderly (PASE) questionnaire. Sum effective load ratings (ELRs) and peak force were estimated from the PASE questionnaire, reflecting the total and highest loading intensity and application rate of physical activities, respectively. Participants were contacted every 4 months over two years to self-report falls, and over 6.0±2.2 years for fractures. Hip fractures were ascertained by data-linkage for 8.9±3.6 years. Compared to sum ELR and PASE scores, peak force demonstrated the greatest standardised effect size for BMD maintenance at the spine (β=9.77mg/cm ), total hip (β=14.14mg/cm ) and femoral neck (β=13.72mg/cm ) after adjustment for covariates, including PASE components (all p<0.01). Only PASE scores were significantly associated with reduced falls risk (standardised incident rate ratio=0.90, 95% confidence interval=0.81-1.00, p=0.04). All physical activity measures were significantly associated with reduced incident fractures in univariate analyses but none remained significant after multivariable adjustments. Older men who engaged in physical activity of high and rapid impact maintained higher BMD, while higher energy expenditure was associated with reduced falls risk. Coupling traditional physical activity data with bone loading estimates may improve understanding of the relationships between physical activity and bone health. This article is protected by copyright. All rights reserved.

MeSH Terms

-

Keywords

Exercise; aging; fracture prevention; general population studies; osteoporosis

Is impaired dopaminergic function associated with mobility capacity in older adults?

Abstract

The capacity to move is essential for independence and declines with age. Slow movement speed, in particular, is strongly associated with negative health outcomes. Prior research on mobility (herein defined as movement slowness) and aging has largely focused on musculoskeletal mechanisms and processes. More recent work has provided growing evidence for a significant role of the nervous system in contributing to reduced mobility in older adults. In this article, we report four pieces of complementary evidence from behavioral, genetic, and neuroimaging experiments that, we believe, provide theoretical support for the assertion that the basal ganglia and its dopaminergic function are responsible, in part, for age-related reductions in mobility. We report four a posteriori findings from an existing dataset: (1) slower central activation of ballistic force development is associated with worse mobility among older adults; (2) older adults with the Val/Met intermediate catecholamine-O-methyl-transferase (COMT) genotype involved in dopamine degradation exhibit greater mobility than their homozygous counterparts; (3) there are moderate relationships between performance times from a series of lower and upper extremity tasks supporting the notion that movement speed in older adults is a trait-like attribute; and (4) there is a relationship of functional connectivity within the medial orbofrontal (mOFC) cortico-striatal network and measures of mobility, suggesting that a potential neural mechanism for impaired mobility with aging is the deterioration of the integrity of key regions within the mOFC cortico-striatal network. These findings align with recent basic and clinical science work suggesting that the basal ganglia and its dopaminergic function are mechanistically linked to age-related reductions in mobility capacity.

MeSH Terms

-

Keywords

Aging; Basal ganglia; Dopamine; Mobility; Neural control; Sarcopenia

The Resistance of [i]Drosophila melanogaster[/i] to Oxidative, Genotoxic, Proteotoxic, Osmotic Stress, Infection, and Starvation Depends on Age According to the Stress Factor.

Abstract

We studied how aging affects the ability of [i]Drosophila melanogaster[/i] to tolerate various types of stress factors. Data were obtained on the resistance of [i]D. melanogaster[/i] to oxidative and genotoxic (separately paraquat, Fe , Cu , and Zn ions), proteotoxic (hyperthermia, Cd ions), and osmotic (NaCl) stresses, starvation, and infection with the pathological [i]Beauveria bassiana[/i] fungus at different ages. In all cases, we observed a strong negative correlation between age and stress tolerance. The largest change in the age-dependent decline in survival occurred under oxidative and osmotic stress. In most experiments, we observed that young [i]Drosophila[/i] females have higher stress resistance than males. We checked whether it is possible to accurately assess the biological age of [i]D. melanogaster[/i] based on an assessment of stress tolerance. We have proposed a new approach for assessing a biological age of [i]D. melanogaster[/i] using a two-parameter survival curve model. For the model, we used an algorithm that evaluated the quality of age prediction for different age and gender groups. The best predictions were obtained for females who were exposed to CdCl and ZnCl with an average error of 0.32 days and 0.36 days, respectively. For males, the best results were observed for paraquat and NaCl with an average error of 0.61 and 0.68 days, respectively. The average accuracy for all stresses in our model was 1.73 days.

MeSH Terms

-

Keywords

Drosophila melanogaster; aging; biomarkers of aging; modeling; stress resistance

Interaction Information Along Lifespan of the Resting Brain Dynamics Reveals a Major Redundant Role of the Default Mode Network.

Abstract

Interaction Information (II) generalizes the univariate Shannon entropy to triplets of variables, allowing the detection of redundant (R) or synergetic (S) interactions in dynamical networks. Here, we calculated II from functional magnetic resonance imaging data and asked whether R or S vary across brain regions and along lifespan. Preserved along lifespan, we found high overlapping between the pattern of high R and the default mode network, whereas high values of S were overlapping with different cognitive domains, such as spatial and temporal memory, emotion processing and motor skills. Moreover, we have found a robust balance between R and S among different age intervals, indicating informational compensatory mechanisms in brain networks.

MeSH Terms

-

Keywords

default mode network; interaction information; lifespan; redundancy; resting state; synergy

Development of normative data for the Five Point Test using the cognitive reliability and time to failure rate theory.

Abstract

In this study, several theoretically based curve fitting nonlinear models for analyzing the Five Point Test (FPT), a nonverbal fluency test, were examined. One thousand two hundred and one participants from the general population of Germany and the USA completed the FPT. The test scores were analyzed using three process indexes; the number of unique designs, strategy, and repetitions. Participants were stratified by age and level of education, and the resulting data were examined using best-fit nonlinear distribution equations. The study shows that the Weibull Growth three-factor curve fitting model provides equivalent fit as four-factor quadratic or linear curve fitting models for estimates continue normative data the Reliability and Time to Failure Theory of Cognitive Functions. Namely, that neurocognitive abilities remain stable during young adulthood and after reaching a threshold, starts to linearly or exponentially decline. The study also shows that education differentially impacts the asymptote, threshold, and decline rate of the FPT indexes confirming the importance of isolating specific cognitive domains within neuropsychological tests as these indexes might be related to the activation of particular cell assemblies, which in turn are differentially impacted by aging.

MeSH Terms

-

Keywords

Aging; nonverbal fluency; reliability theory

Can Melatonin Be a Potential "Silver Bullet" in Treating COVID-19 Patients?

Abstract

The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Moreover, indirect evidence points out to a possible antiviral action of melatonin by interfering with SARS-CoV-2/angiotensin-converting enzyme 2 association. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. As a cytoprotector, melatonin serves to combat several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease. In view of evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. Since melatonin is an effective means to control cognitive decay in minimal cognitive impairment, its therapeutic significance for the neurological sequels of SARS-CoV-2 infection should be considered. Finally, yet importantly, exogenous melatonin can be an adjuvant capable of augmenting the efficacy of anti-SARS-CoV-2 vaccines. We discuss in this review the experimental evidence suggesting that melatonin is a potential "silver bullet" in the COVID 19 pandemic.

MeSH Terms

-

Keywords

COVID-19 pandemic; aging; anti-SARS-CoV-2 vaccination; chronotherapy; cognitive impairment; cytoprotection; diabetes; inflammation; melatonin; metabolic syndrome; neurodegeneration; oxidative stress; renin–angiotensin system

Shorter telomere length of white blood cells is associated with higher rates of aneuploidy among infertile women undergoing in vitro fertilization.

Abstract

To evaluate whether the telomere length of white blood cells (WBC) and cumulus cells (CC) in an infertile population is associated with ovarian and embryonic performance. Prospective cohort study. Academic-affiliated private practice. A total of 175 infertile women undergoing in vitro fertilization (IVF) at a single center between July 2017 and December 2018. On the day of oocyte retrieval, genomic DNA was isolated from WBC and CC samples. Telomere length assessment was performed for both tissue types using quantitative real-time polymerase chain reaction. Telomere lengths were normalized using an AluYa5 sequence as an endogenous control, and linear regressions were applied. This study assessed the relationship between relative telomere length of WBC and CC samples and measures of ovarian and embryonic performance. Specifically, patient age, antimüllerian hormone (AMH) level, peak estradiol (E ) level, number of oocytes retrieved, number of mature (MII) oocytes retrieved, blastulation rate, and aneuploidy rate were assessed. There was a statistically significant relationship between WBC relative telomere length and patient age as well as rates of embryonic aneuploidy, with shorter WBC relative telomere length associated with increasing patient age (P<.01) and higher rates of aneuploidy (P=.01). No statistically significant relationships were observed between WBC relative telomere length and the other outcome measures. No significant associations were noted between CC relative telomere length and any outcomes assessed in this study. The relationship between WBC relative telomere length and aneuploidy warrants further investigation, particularly because significant overlap exists between increasing maternal age and rates of embryonic aneuploidy.

MeSH Terms

-

Keywords

Cumulus cells; female infertility; ovarian biology; reproductive aging; telomere length

Therapy-induced polyploidization and senescence: Coincidence or interconnection?

Abstract

Polyploid somatic cells have 'programmed' roles in normal development and stress responses. Transient polyploidy states have been observed in several tumor types at early stages of tumorigenesis. They can give rise to the aneuploidy state which is a common feature of human cancer cells. Similarly, to cancer development, cancer treatment can lead to transient polyploidy. Polyploid giant cells (PGCCs) in cancer are often associated with poor prognosis and disease relapse. Cancer cell senescence- a proliferation arrest accompanied by a set of characteristic markers- induced by therapy is also associated with transient polyploidy formation and cancer relapse. The question is whether therapy-induced senescence (TIS) and therapy induced polyploidy (TIP) are mechanistically or coincidentally connected. This problem needs to be solved rather urgently, because TIS appears to be more common phenomena than originally believed. Another arising question concerns reversibility of cancer cell senescence as a consequence of atypical divisions of polyploid cells. In our review we will try to answer this fundamental question by referring to published literature and to our own studies.

MeSH Terms

-

Keywords

Amitotic divisions; PGCCs; Senescence escape; Therapy-induced senescence

Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence.

Abstract

Cancer treatment has been associated with accelerated aging that can lead to early-onset health complications typically experienced by older populations. In particular, cancer survivors have an increased risk of developing premature cardiovascular complications. In the last two decades, cellular senescence has been proposed as an important mechanism of premature cardiovascular diseases. Cancer treatments, specifically anthracyclines and radiation, have been shown to induce senescence in different types of cardiovascular cells. Additionally, clinical studies identified increased systemic markers of senescence in cancer survivors. Preclinical research has demonstrated the potential of several approaches to mitigate cancer therapy-induced senescence. However, strategies to prevent and/or treat therapy-induced cardiovascular senescence have not yet been translated to the clinic. In this review, we will discuss how therapy-induced senescence can contribute to cardiovascular complications. Thereafter, we will summarize the current in vitro, in vivo, and clinical evidence regarding cancer therapy-induced cardiovascular senescence. Then, we will discuss interventional strategies that have the potential to protect against therapy-induced cardiovascular senescence. To conclude, we will highlight challenges and future research directions to mitigate therapy-induced cardiovascular senescence in cancer survivors.

MeSH Terms

-

Keywords

Senescence; cancer therapy; cardio-oncology; cardiotoxicity; cardiovascular diseases; doxorubicin; radiation

"Building the Threads of Connection that We Already Have": The Nature of Connections via Technology for Older People.

Abstract

The social connectedness of older people is of increasing concern. Technology has been suggested for enhancing social inclusion. This study aimed to explore the nature and quality of connections via technology.  : Qualitative exploration of experiences, stories, and needs was undertaken through semi-structured interviews with older (7) and middle-aged (3) adults with rich experience of connections via technology in Australia and England. Core aspects of connections through technology were constructed through interpretive description analysis.  : Four key aspects were: 1. [i]The caliber of connections[/i]: descriptions of a range of subjective quality of connections and characteristics of good connections; 2. Experiences of poor connection ([i]mis- and dis-connection[/i]) including descriptions of experiences creating isolation; 3. [i]Reasons to connect[/i] described the purposes of technology-based connections including connecting with others, themselves and places important to them; 4. [i]Making connections work[/i] described active strategies to enhance connection.  : Using technology is part of the social engagement of many people. Considering the related feelings of connection and support strategies and needs could enhance future research and practice with older people.  : The different characteristics and potential positive and negative experiences of connection via technology need consideration in measuring social isolation and supporting older adults.

MeSH Terms

-

Keywords

Aging; isolation; loneliness; social; social technology

Validation of the Dépistage Cognitif de Québec in the Oldest Old.

Abstract

We aimed to validate the [i]Dépistage Cognitif de Québec[/i] (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical degenerative syndromes, in the oldest old. The DCQ was developed by expert behavioural neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioural variant frontotemporal dementia. It targets five relevant cognitive domains: Memory, Visuospatial, Executive, Language, and Behaviour. Validation was performed using a prospective community-based sample consisting of 53 healthy French-speaking Canadian volunteers aged between 80 and 94 years old. Normative data were derived from participants with no history of cognitive difficulties and a Montreal Cognitive Assessment (MoCA) score ≥ 24. The mean DCQ total score (out of 100) was 84.65 (SD = 6.33). Pearson's correlation coefficient showed a moderate, but significant, correlation ([i]r[/i] = 0.36, [i]p[/i] < .01) with the MoCA. Normative data shown in percentiles were stratified by age and education for DCQ total score and for each of the five cognitive domains. This study suggests that the DCQ is a valid cognitive screening test in the oldest old. It is proposed that the DCQ can help early identification of atypical degenerative syndromes.

MeSH Terms

-

Keywords

Alzheimer’s disease; aging; atypical dementia; dementia; frontotemporal dementia; normative data; oldest old; test construction; validation

Comorbidity Patterns of Older Lung Cancer Patients in Northeast China: An Association Rules Analysis Based on Electronic Medical Records.

Abstract

This study aims to identify the comorbidity patterns of older men with lung cancer in China. We analyzed the electronic medical records (EMRs) of lung cancer patients over age 65 in the Jilin Province of China. The data studied were obtained from 20 hospitals of Jilin Province in 2018. In total, 1510 patients were identified. We conducted a rank-frequency analysis and social network analysis to identify the predominant comorbidities and comorbidity networks. We applied the association rules to mine the comorbidity combination with the values of confidence and lift. A heatmap was utilized to visualize the rules. Our analyses discovered that (1) there were 31 additional medical conditions in older patients with lung cancer. The most frequent comorbidities were pneumonia, cerebral infarction, and hypertension. (2) The network-based analysis revealed seven subnetworks. (3) The association rules analysis provided 41 interesting rules. The results revealed that hypertension, ischemic cardiomyopathy, and pneumonia are the most frequent comorbid combinations. Heart failure may not have a strong implicating role in these comorbidity patterns. Cerebral infarction was rarely combined with other diseases. In addition, glycoprotein metabolism disorder comorbid with hyponatremia or hypokalemia increased the risk of anemia by more than eight times in older lung cancer patients. This study provides evidence on the comorbidity patterns of older men with lung cancer in China. Understanding the comorbidity patterns of older patients with lung cancer can assist clinicians in their diagnoses and contribute to developing healthcare policies, as well as allocating resources.

MeSH Terms

-

Keywords

aging; association rules; chronic disease management; comorbidity; lung cancer

Inhibition of NADPH Oxidases Activity by Diphenyleneiodonium Chloride as a Mechanism of Senescence Induction in Human Cancer Cells.

Abstract

NADPH oxidases (NOX) are commonly expressed ROS-producing enzymes that participate in the regulation of many signaling pathways, which influence cell metabolism, survival, and proliferation. Due to their high expression in several different types of cancer it was postulated that NOX promote tumor progression, growth, and survival. Thus, the inhibition of NOX activity was considered to have therapeutic potential. One of the possible outcomes of anticancer therapy, which has recently gained much interest, is cancer cell senescence. The induction of senescence leads to prolonged inhibition of proliferation and contributes to tumor growth restriction. The aim of our studies was to investigate the influence of low, non-toxic doses of diphenyleneiodonium chloride (DPI), a potent inhibitor of flavoenzymes including NADPH oxidases, on p53-proficient and p53-deficient HCT116 human colon cancer cells and MCF-7 breast cancer cells. We demonstrated that the temporal treatment of HCT116 and MCF-7 cancer cells (both p53 wild-type) with DPI caused induction of senescence, that was correlated with decreased level of ROS and upregulation of p53/p21 proteins. On the contrary, in the case of p53-/- HCT116 cells, apoptosis was shown to be the prevailing effect of DPI treatment. Thus, our studies provided a proof that inhibiting ROS production, and by this means influencing ROS sensitive pathways, remains an alternative strategy to facilitate so called therapy-induced senescence in cancers.

MeSH Terms

-

Keywords

DPI; NADPH oxidases; ROS; apoptosis; cancer; senescence

Advanced old age as a developmental dilemma: An in-depth comparison of established fourth age conceptualizations.

Abstract

Distinguishing the Fourth Age (FoA) from the Third Age (ThA) has become a common practice in aging research. In this theoretical paper, we focus on four established conceptualizations of the ThA-FoA distinction, i.e., (1) Neugarten's work on the young-old vs. the old-old; (2) Laslett's concept of the innovative life period of the ThA; (3) Erikson's 9th life stage approach; and (4) Baltes' approach considering the FoA as the most radical incompleteness of the human condition. After a comparative descriptive analysis, we extract evaluative elements inherent in the four approaches according to six categories: (1) fundamental values; (2) positive evaluative elements; (3) negative evaluative elements; (4) the decline vs. growth view; (5) the continuity vs. discontinuity view; and (6) values related to practical issues. As an overarching result of our analysis, we conclude that all conceptions face - in different ways - dilemmas that seem difficult to solve. One option may be to give up all ambitions toward agency for the FoA and indeed qualify this phase as the "aging without agency" phase of life. Doing so, however, seems ethically questionable, because it would give up acknowledged values connected with a good human life such as human goal-directed autonomy and freedom. In conclusion, the ThA-FoA distinction, although arguably a needed and helpful roadmap for the recent decades of aging science, comes with enduring disadvantages and eventually even risks. Therefore, in future aging science, we recommend avoiding the ThA-FoA distinction or at least using it only in combination with a critical attitude.

MeSH Terms

-

Keywords

Agency and aging; Ethics of aging; Fourth age; Third age; Young-old vs. old-old

Photoacclimation to high-light stress in Chlamydomonas reinhardtii during conditional senescence relies on generating pH-dependent, high-quenching centres.

Abstract

Microalgae can respond to long-term increases in light intensity by altering the concentration of photosynthetic complexes. Under active growth, the ability of Chlamydomonas reinhardtii to acclimate to excess light is dependent on cell division to reduce the concentration of photosynthetic complexes. But, in batch culture, cells eventually reach stationary phase where their ability to divide is limited; this should impact their capacity to undergo photoacclimation. Our goal is to dissect excess-light responses as cells approach stationary phase and to determine how the strategies of photoacclimation differ compared to cells in the exponential-growth phase. In this study, cultures exited exponential growth and transitioned into a declining growth phase (DGP), where cells continued a slow rate of growth for the next seven days in both low (LL) and high-light (HL). During this period, both cultures experience a conditional senescence-related decline in chlorophyll levels. Under HL, however, the senescing cultures have a rapid decline in PSII reaction centres, maintain a stable concentration of LHCII antenna, rapidly increase LHCSR levels, and have a sustained increase in Fo/Fm. Collectively this implies that the remaining antenna act as pH-dependent, quenching centres, presumably to protect the senescing chloroplast against HL. We discovered that acclimating to HL post-exponential phase involves active degradation that is intertwined with the normal senescence process that allowed for a limited rate of cell division.

MeSH Terms

-

Keywords

Autophagy; Chlamydomonas; Conditional senescence; LHCSR; NPQ; Photoacclimation

Characterizing Experiences of Conversion Therapy Among Middle-Aged and Older Men Who Have Sex with Men from the Multicenter AIDS Cohort Study (MACS).

Abstract

Conversion therapies are practices that attempt to change an individuals' same-sex attractions through psychotherapeutic and aversive therapeutic techniques. Conversion therapies were developed based on homophobic beliefs that same-sex attractions are a mental illness. We sought to describe the prevalence and characteristics of conversion therapy experienced among middle-aged and older men who have sex with men in the United States. Given associations of homophobic stigma and HIV risk, we hypothesized that HIV-positive men would report higher odds of conversion therapy compared to HIV-negative men. We analyzed data from 1,237 middle-aged and older MSM enrolled in the Multicenter AIDS Cohort Study. Among participants, 17.7% reported lifetime conversion therapy, of which the average start of therapy age was 22.67 ([i]sd[/i] = 10.56) years, 25.8% reported therapy durations of 6+ months, 37.7% reported session frequencies 1+ session per week, and 35.9% indicated that undergoing therapy was either a little or not at all their decision. We observed no statistically significant association between reporting lifetime conversion therapy and HIV status. Future efforts should continue to assess the magnitude of harm conversion therapies impose on MSM's health across the life course as well as test potential, indirect associations that may link these practices to HIV.

MeSH Terms

-

Keywords

Aging; Conversion Therapy; Gay and Bisexual Men; HIV; Stigma

The Process of Creating and Disseminating Exercise Programs by Physical Therapists for Older Adults With Chronic Back Pain.

Abstract

The purpose of this study was to enhance the understanding of the process that physical therapists undertake when creating and disseminating exercise programs for older adults with chronic back pain. Constructivist grounded theory methodology was used as an accessible mode of researching pragmatic clinical practices. Physical therapists from outpatient, ambulatory care clinic settings participated in in-depth, individual interviews (n = 9) and in-clinic observations (n = 5). Data collection and analysis were iterative processes. Codes were generated based on recurrent themes, and constant comparative analysis was used to compare data. Analysis and data collection were concluded when theoretical sufficiency was reached. Physical therapist participants described the process of creating and implementing exercise plans as involving listening to the patient's story, determining function, physical therapy care, supported integration, and, ultimately, returning back to living and life with chronic back pain. Participants worked through the 5 phases at different rates, often recurrently, when treating older adults with chronic back pain. The phases are positioned within a shared alliance between physiotherapy provider and patient, with a transfer of responsibility occurring throughout treatment and follow-up sessions, progressing toward patient independence. This transfer of responsibility served as the core category for the process herein. This research highlights the importance of listening to patients' stories when engaging in physical therapy care. Focusing on function, providing education and exercise as components of care, and supporting integration of exercise into everyday life are considerations for providing care for older adults with chronic back pain in physical therapist practice, and, ultimately, for returning to life. With aging populations and with the increasing prevalence of chronic conditions, this research offers insight into a process for physical therapists to enact exercise engagement for improved health and quality of life for older adults with chronic back pain.

MeSH Terms

-

Keywords

Aging; Back Pain; Chronic Pain; Exercise; Older Adults; Physical Activity

Aging and leukemic evolution of hematopoietic stem cells under various stress conditions.

Abstract

Hematopoietic stem cells (HSCs) have self-renewal capacity and differentiation potential into all lineages of blood cells throughout the lifetime of an organism. The function of HSCs gradually changes during aging. To date, various stress factors influencing HSC aging have been identified. The increased production of reactive oxygen species and DNA damage responses are causatively attributed to HSC aging. The increased apolarity is a prominent feature of aged HSCs, whereas it is less obvious in young HSCs. The bone marrow (BM) microenvironment niche is a crucial factor for HSC aging. Mesenchymal stem cells show skewed differentiation during aging, which leads to decreased bone formation and increased adipogenesis. The accumulation of adipocytes confers negative effects on hematopoiesis. Loss of sympathetic nerve fibers or adrenoreceptor β3 signaling induces premature HSC and niche aging. Epigenetic regulators such as polycomb group proteins and the sirtuin family of proteins act to prevent premature aging. Targeting these factors, several rejuvenation strategies for aged HSCs have been employed in mice. However, we still do not know whether these strategies can be extrapolated to human HSCs. Aging is frequently accompanied by the development of clonal hematopoiesis, which is called age-related clonal hematopoiesis (ARCH) or clonal hematopoiesis of indeterminate potential (CHIP). Most ARCH/CHIP mutations occur in genes encoding epigenetic regulators including DNMT3A, TET2, and ASXL1, which suggests the relevance of epigenetic drift during the aging process. ARCH/CHIP is a strong risk factor for subsequent hematologic cancer. Notably, it also has an impact on the development of non-malignant disorders such as coronary heart disease. Further studies are warranted to decipher the complete picture of molecular crosstalk that regulates HSC aging.

MeSH Terms

-

Keywords

Age-related clonal hematopoiesis; Aging; Clonal hematopoiesis of indeterminate potential; DNA damage; Epigenetics; Hematopoietic stem cell; Polarity; Reactive oxygen species; Senescence; Stem cell niche

Modeling Retest Effects in a Longitudinal Measurement Burst Study of Memory.

Abstract

Longitudinal designs must deal with the confound between increasing age and increasing task experience (i.e., retest effects). Most existing methods for disentangling these factors rely on large sample sizes and are impractical for smaller scale projects. Here, we show that a measurement burst design combined with a model of retest effects can be used to study age-related change with modest sample sizes. A combined model of age-related change and retest-related effects was developed. In a simulation experiment, we show that with sample sizes as small as [i]n[/i] = 8, the model can reliably detect age effects of the size reported in the longitudinal literature while avoiding false positives when there is no age effect. We applied the model to data from a measurement burst study in which eight subjects completed a burst of seven sessions of free recall every year for five years. Six additional subjects completed a burst only in years 1 and 5. They should, therefore, have smaller retest effects but equal age effects. The raw data suggested slight improvement in memory over five years. However, applying the model to the yearly-testing group revealed that a substantial positive retest effect was obscuring stability in memory performance. Supporting this finding, the control group showed a smaller retest effect but an equal age effect. Measurement burst designs combined with models of retest effects allow researchers to employ longitudinal designs in areas where previously only cross-sectional designs were feasible.

MeSH Terms

-

Keywords

aging; free recall; memory models; practice effects; stability

Reactive, Agentic, Apathetic, or Challenged? Aging, Emotion, and Coping During the COVID-19 Pandemic.

Abstract

Advanced age is generally associated with improved emotional well-being, but the COVID-19 pandemic unleashed a global stressor that gravely threatened the physical well-being and ostensibly challenged the emotional well-being of older adults disproportionately. The current study investigated differences in emotional experiences and coping strategies between younger and older adults during the pandemic, and whether these differences were accounted for by age differences in appraisal of the pandemic. We asked younger (n = 181) and older adult (n = 176) participants to report their stress, appraisals the pandemic, emotions, and the ways in which they were coping with the pandemic. Results indicated that older adults experienced less stress and less negative affect and used greater problem-focused coping and less avoidant coping in response to the pandemic than younger adults. Further, age differences in affect and coping were partially accounted for by age differences in appraisals of the pandemic. Despite their objectively higher risk of illness and death due to the pandemic, older adults experienced less negative affect and used more agentic coping strategies than younger adults.

MeSH Terms

-

Keywords

affect; aging; appraisal; chronic stress; emotion regulation

Aligning social and health care services: The case of Community Care Connections.

Abstract

The Community Care Connections (CCC) program aims to align social and healthcare services to improve health outcomes in older adults with complex medical and social needs. This study assessed changes in healthcare utilization before and after CCC program participation. Between June 2016 and March 2019, 1214 adults with complete data who provided informed consent participated in the CCC program. CCC client data were linked with data on hospitalizations, emergency department (ED) visits, and observation stays 90 days before and after program start. Data analysis examined changes in health care utilization 90 days after program start, compared to 90 days before. Hospitalizations decreased by 30% (Change = -0.029, 95% Confidence Interval (CI) = -0.053, -0.005), ED visits decreased by 29% (Change = -0.114, 95% CI = -0.163, -0.066), and observation stays decreased by 23% (Change = -0.041, 95% CI = -0.073, -0.009) during the post period. ED visits decreased by 37% (Change = -0.140, 95% CI = -0.209, -0.070) for those with hypertension and by 30% (Change = -0.109, 95% CI = -0.199, -0.020) for those with high cholesterol, while observation stays decreased by 46% (Change = -0.118, 95% CI = -0.185, -0.052) for those with diabetes and by 44% (Change = -0.082, 95% CI = -0.150, -0.014) for those with high cholesterol during the post period. Connecting older adults with social services through the healthcare delivery system may lead to decreases in hospitalizations, ED visits, and observation stays. Implementation of cross-sector partnerships that address non-clinical factors that impact the health of older adults may reduce the use of costly healthcare services.

MeSH Terms

-

Keywords

Aging services; Healthcare utilization; Population health; Program evaluation; Social determinants; Social services

Analysis of Stored mRNA Degradation in Acceleratedly Aged Seeds of Wheat and Canola in Comparison to Arabidopsis.

Abstract

Seed aging has become a topic of renewed interest but its mechanism remains poorly understood. Our recent analysis of stored mRNA degradation in aged Arabidopsis seeds found that the stored mRNA degradation rates (estimated as the frequency of breakdown per nucleotide per day or [i]β[/i] value) were constant over aging time under stable conditions. However, little is known about the generality of this finding to other plant species. We expanded the analysis to aged seeds of wheat ([i]Triticum aestivum[/i]) and canola ([i]Brassica napus[/i]). It was found that wheat and canola seeds required much longer periods than Arabidopsis seeds to lose seed germination ability completely under the same aging conditions. As what had been observed for Arabidopsis, stored mRNA degradation (∆Ct value in qPCR) in wheat and canola seeds correlated linearly and tightly with seed aging time or mRNA fragment size, while the quality of total RNA showed little change during seed aging. The generated [i]β[/i] values reflecting the rate of stored mRNA degradation in wheat or canola seeds were similar for different stored mRNAs assayed and constant over seed aging time. The overall [i]β[/i] values for aged seeds of wheat and canola showed non-significant differences from that of Arabidopsis when aged under the same conditions. These results are significant, allowing for better understanding of controlled seed aging for different species at the molecular level and for exploring the potential of stored mRNAs as seed aging biomarkers.

MeSH Terms

-

Keywords

canola; real-time quantitative PCR (qPCR); seed aging; seed germination; seed longevity; stored mRNA degradation; wheat; β value

[AEDG peptide regulates human circadian rhythms genes expression during pineal gland accelerated aging.]

Abstract

Night work provides biorhythms desynchronization, disorder of melatonin-producing function and accelerated pineal gland aging. One of the promising geroprotectors restoring the pineal melatonin synthesis is the AEDG (Ala-Glu-Asp-Gly) peptide. AEDG peptide increases in 1,7 times the 6-sulfatoxymelatonin (6-SOMT) excretion in the urine of middle-aged people. Moreover, AEDG peptide normalized circadian Clock and Csnk1e genes hyper expression in leukocytes in 1,9-2,1 times and increases the Cry2 gene hypo expression in peripheral blood lymphocytes in 2 times in people with reduced melatonin-producing epiphysis function. The geroprotective effect of the AEDG peptide is based on its ability to restore the epiphysis melatonin-producing function by means regulation of human circadian genes expression.

MeSH Terms

-

Keywords

AEDG peptide; accelerated aging; circadian genes; melatonin; pineal gland

Dietary protein intake and circulating advanced glycation end product/receptor for advanced glycation end product concentrations in the Health, Aging, and Body Composition Study.

Abstract

Advanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking. We examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black). CML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors. CML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio. Higher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

MeSH Terms

-

Keywords

advanced glycation end products; aging; chronic kidney disease; dietary protein; soluble receptor for advanced glycation end products; type 2 diabetes

Cellular senescence as a response to multiwalled carbon nanotube (MWCNT) exposure in human mesothelial cells.

Abstract

Cellular senescence is a stable cell cycle arrest induced by diverse triggers, including replicative exhaustion, DNA damaging agents, oncogene activation, oxidative stress, and chromatin disruption. With important roles in aging and tumor suppression, cellular senescence has been implicated also in tumor promotion. Here we show that certain multiwalled carbon nanotubes (MWCNTs), as fiber-like nanomaterials, can trigger cellular senescence in primary human mesothelial cells. Using in vitro approaches, we found manifestation of several markers of cellular senescence, especially after exposure to a long and straight MWCNT. These included inhibition of cell division, senescence-associated heterochromatin foci, senescence-associated distension of satellites, LMNB1 depletion, γH2A.X nuclear panstaining, and enlarged cells exhibiting senescence-associated β-galactosidase activity. Furthermore, genome-wide transcriptome analysis revealed many differentially expressed genes, among which were genes encoding for a senescence-associated secretory phenotype. Our results clearly demonstrate the potential of long and straight MWCNTs to induce premature cellular senescence. This finding may find relevance in risk assessment of workplace safety, and in evaluating MWCNT's use in medicine such as drug carrier, due to exposure effects that might prompt onset of age-related diseases, or even carcinogenesis.

MeSH Terms

-

Keywords

alpha tubulin; cellular senescence; mesothelial cells; microarray analysis; multiwalled carbon nanotubes; γH2A.X

Effect of cellular and ECM aging on human iPSC-derived cardiomyocyte performance, maturity and senescence.

Abstract

Cardiovascular diseases are the leading cause of death worldwide and their occurrence is highly associated with age. However, lack of knowledge in cardiac tissue aging is a major roadblock in devising novel therapies. Here, we studied the effects of cell and cardiac extracellular matrix (ECM) aging on the induced pluripotent stem cell (iPSC)-derived cardiomyocyte cell state, function, as well as response to myocardial infarction (MI)-mimicking stress conditions in vitro. Within 3-weeks, young ECM promoted proliferation and drug responsiveness in young cells, and induced cell cycle re-entry, and protection against stress in the aged cells. Adult ECM improved cardiac function, while aged ECM accelerated the aging phenotype, and impaired cardiac function and stress defense machinery of the cells. In summary, we have gained a comprehensive understanding of cardiac aging and highlighted the importance of cell-ECM interactions. This study is the first to investigate the individual effects of cellular and environmental aging and identify the biochemical changes that occur upon cardiac aging.

MeSH Terms

-

Keywords

Cardiac aging; Cardiac tissue engineering; Decellularized extracellular matrix; Human induced pluripotent stem cell-derived cardiomyocyte; Hypoxia; Myocardial infarction

Older People's Use and Nonuse of the Internet in Sweden.

Abstract

The use of the internet has considerably increased over recent years, and the importance of internet use has also grown as services have gone online. Sweden is largely an information society like other countries with high reported use amongst European countries. In line with digitalization development, society is also changing, and many activities and services today take place on the internet. This development could potentially lead to those older persons who do not use the internet or do not follow the development of services on the internet finding it difficult to take part in information and activities that no longer occur in the physical world. This has led to a digital divide between groups, where the older generations (60+), in particular, have been affected. In a large study of Sweden's adult population in 2019, 95 percent of the overall population was said to be internet users, and the corresponding number for users over 66 years of age was 84%. This study shows that the numbers reported about older peoples' internet use, most likely, are vastly overestimated and that real use is significantly lower, especially among the oldest age groups. We report that 62.4% of the study subjects are internet users and that this number most likely also is an overestimation. When looking at nonresponders to the questionnaire, we find that they display characteristics generally attributed to non-use, such as lower education, lower household economy, and lower cognitive functioning.

MeSH Terms

-

Keywords

aging; gerontechnology; internet; usage

P53 induces senescence in the unstable progeny of aneuploid cells.

Abstract

Aneuploidy is the condition of having an imbalanced karyotype, which is associated with tumor initiation, evolution, and acquisition of drug-resistant features, possibly by generating heterogeneous populations of cells with distinct genotypes and phenotypes. Multicellular eukaryotes have therefore evolved a range of extrinsic and cell-autonomous mechanisms for restraining proliferation of aneuploid cells, including activation of the tumor suppressor protein p53. However, accumulating evidence indicates that a subset of aneuploid cells can escape p53-mediated growth restriction and continue proliferating [i]in vitro[/i]. Here we show that such aneuploid cell lines display a robust modal karyotype and low frequency of chromosomal aberrations despite ongoing chromosome instability. Indeed, while these aneuploid cells are able to survive for extended periods [i]in vitro[/i], their chromosomally unstable progeny remain subject to p53-induced senescence and growth restriction, leading to subsequent elimination from the aneuploid pool. This mechanism helps maintain low levels of heterogeneity in aneuploid populations and may prevent detrimental evolutionary processes such as cancer progression and development of drug resistance.

MeSH Terms

-

Keywords

P53; aneuploidy; genome instability; senescence

Asiatic acid protects oocytes against [i]in vitro[/i] aging-induced deterioration and improves subsequent embryonic development in pigs.

Abstract

As a pentacyclic triterpene in [i]Centella asiatica[/i], asiatic acid (AA) is a powerful antioxidant with many bioactivities. In the present research, we investigated whether AA has the potential to rescue the decrease in porcine oocyte quality that occurs during [i]in vitro[/i] aging (IVA). Mature porcine oocytes were collected and then continuously cultured for an additional 24 h or 48 h with or without AA in maturation medium as an IVA model. The results revealed that AA supplementation reduced the percentage of abnormal aged porcine oocytes during IVA. Furthermore, AA supplementation effectively maintained aged porcine oocyte developmental competence, both parthenogenetic activation and [i]in vitro[/i] fertilization. The number of sperm that bound to the zona pellucida on aged porcine oocytes was higher in the AA-supplemented group than in the non-supplemented group. Moreover, AA supplementation not only blocked IVA-induced oxidative stress but also maintained intracellular GSH levels and reduced the percentage of early apoptosis aged porcine oocytes. Mitochondrial functions were disordered during the IVA process. The intracellular ATP levels and mitochondrial membrane potential in aged porcine oocytes were dramatically increased by AA supplementation. Therefore, AA has beneficial effects on porcine oocyte quality and developmental potential maintenance during IVA.

MeSH Terms

-

Keywords

asiatic acid; early embryonic development; oocyte aging; oxidative stress; pig

Family care across diverse cultures: Re-envisioning using a transnational lens.

Abstract

In an increasingly globalized world, the importance of developing a more culturally complex understanding of family care has been clearly identified. This study explored family care across three different cultural groups - Chinese, South Asian, and Latin American - living in a metropolitan, Pacific-West, Canadian city. In-depth qualitative interviews were conducted with 29 family members from one of the three family groups exploring how they practiced 'care' for their aging, often frail, relatives. The importance of conceptualizing family care as a transnational, collective undertaking emerged from the outset as critical for understanding care practices in all three cultural communities. Three themes identified contributed to this conceptualization: the need to broaden the understanding of family care; the centrality of geographic mobility, and the need to rethink the location of aging and consider its relationship to mobility; and the use of technology by extended family networks to facilitate continuity and connection. An over-riding notion of 'flow' or fluid movement, rather than a fixed, static arrangement, emerged as critical for understanding family care. This perspective challenges the dominant approach to studying family care in gerontology that generally conceptualizes family care practice as one local primary caregiver, often female, with some support from other family members. Understanding family care from a transnational lens builds support for the importance of a feminist Ethics of Care lens and has important implications for policy and service delivery practices.

MeSH Terms

-

Keywords

Culture; Ethics of care; Family care; Flow of care; Technology; Transnational aging

Clinical Role of Lung Ultrasound for the Diagnosis and Prognosis of Coronavirus Disease Pneumonia in Elderly Patients: A Pivotal Study.

Abstract

Lung ultrasound (LUS) showed a promising role in the diagnosis and monitoring of patients hospitalized for novel coronavirus disease (COVID-19). However, no data are available on its role in elderly patients. The aim of this study was to evaluate the diagnostic and prognostic role of LUS in elderly patients hospitalized for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia. Consecutive elderly patients (age >65 years) hospitalized for COVID-19 were enrolled. Demographics, laboratory, comorbidity, and the clinical features of the patients were collected. All patients underwent LUS on admission to the ward. LUS characteristics have been analyzed. Uni- and multivariate analyses to evaluate predictors for in-hospital death were performed. Thirty-seven hospitalized elderly patients (19 men) with a diagnosis of SARS-CoV-2 infection were consecutively enrolled. The median age was 82 years (interquartile range 74.5-93.5). Ultrasound alterations were found in all patients enrolled; inhomogeneous interstitial syndrome with spared areas (91.9%) and pleural alterations (100%) were the most frequent findings. At univariate analysis, LUS score (hazard ratio [HR] 1.168, 95% CI 1.049-1.301) and pleural effusions (HR 3.995, 95% CI 1.056-15.110) were associated with in-hospital death. At multivariate analysis, only LUS score (HR 1.168, 95% CI 1.049-1.301) was independelty associated with in-hospital death. The LUS score's best cutoff for distinguishing patients experiencing in-hospital death was 17 (at multivariate analysis LUS score ≥17, HR 4.827, 95% CI 1.452-16.040). In-hospital death was significantly different according to the LUS score cutoff of 17 (p = 0.0046). LUS could play a role in the diagnosis and prognosis in elderly patients hospitalized for SARS-CoV-2 infection.

MeSH Terms

-

Keywords

Aging; Coronavirus disease; Elderly; Lung ultrasound; Severe acute respiratory syndrome-coronavirus-2

Stressful development: Integrating endoderm development, stress, and longevity.

Abstract

In addition to performing digestion and nutrient absorption, the intestine serves as one of the first barriers to the external environment, crucial for protecting the host from environmental toxins, pathogenic invaders, and other stress inducers. The gene regulatory network (GRN) governing embryonic development of the endoderm and subsequent differentiation and maintenance of the intestine has been well-documented in C. elegans. A key regulatory input that initiates activation of the embryonic GRN for endoderm and mesoderm in this animal is the maternally provided SKN-1 transcription factor, an ortholog of the vertebrate Nrf-1 and -2, which, like C. elegans SKN-1, perform conserved regulatory roles in mediating a variety of stress responses across metazoan phylogeny. Other key regulatory factors in early gut development also participate in stress response as well as in innate immunity and aging and longevity. In this review, we discuss the intersection between genetic nodes that mediate endoderm/intestine differentiation and regulation of stress and homeostasis. We also consider how direct signaling from the intestine to the germline, in some cases involving SKN-1, facilitates heritable epigenetic changes, allowing transmission of adaptive stress responses across multiple generations. These connections between regulation of endoderm/intestine development and stress response mechanisms suggest that varying selective pressure exerted on the stress response pathways may influence the architecture of the endoderm GRN, thereby leading to genetic and epigenetic variation in early embryonic GRN regulatory events.

MeSH Terms

-

Keywords

Caenorhabditis elegans; Embryonic development; Epigenetics inheritance; Innate immunity; Longevity; Pleiotropy; Stress

Cause and effect in epigenetics - where lies the truth, and how can experiments reveal it? Epigenetic self-reinforcing loops obscure causation in cancer and aging.

Abstract

Epigenetic changes are implicated in aging and cancer. Sometimes, it is clear whether the causing agent of the condition is a genetic factor or epigenetic. In other cases, the causative factor is unclear, and could be either genetic or epigenetic. Is there a general role for epigenetic changes in cancer and aging? Here, I present the paradigm of causative roles executed by epigenetic changes. I discuss cases with clear roles of the epigenome in cancer and aging, and other cases showing involvement of other factors. I also present the possibility that sometimes causality is difficult to assign because of the presence of self-reinforcing loops in epigenetic regulation. Such loops hinder the identification of the causative factor. I provide an experimental framework by which the role of the epigenome can be examined in a better setting and where the presence of such loops could be investigated in more detail.

MeSH Terms

-

Keywords

aging; cancer; causality; epigenetics; histone modification; methylation; self reinforcing loops

Muscle-specific TGR5 overexpression improves glucose clearance in glucose-intolerant mice.

Abstract

TGR5, a G protein-coupled bile acid receptor, is expressed in various tissues and regulates several physiological processes. In the skeletal muscle, TGR5 activation is known to induce muscle hypertrophy; however, the effects on glucose and lipid metabolism are not well understood, despite the fact that the skeletal muscle plays a major role in energy metabolism. Here, we demonstrate that skeletal muscle-specific TGR5 transgenic (Tg) mice exhibit increased glucose utilization, without altering the expression of major genes related to glucose and lipid metabolism. Metabolite profiling analysis by CE-TOF MS showed that glycolytic flux was activated in the skeletal muscle of Tg mice, leading to an increase in glucose utilization. Upon long-term, high-fat diet (HFD) challenge, blood glucose clearance was improved in Tg mice without an accompanying increase in insulin sensitivity in skeletal muscle and a reduction of body weight. Moreover, Tg mice showed improved age-associated glucose intolerance. These results strongly suggest that TGR5 ameliorated glucose metabolism disorder that is caused by diet-induced obesity and aging by enhancing the glucose metabolic capacity of skeletal muscle. Our study demonstrates that TGR5 activation in the skeletal muscle is effective in improving glucose metabolism and may be beneficial in developing a novel strategy for the prevention or treatment of hyperglycemia.

MeSH Terms

-

Keywords

G protein-coupled receptor (GPCR); TGR5; aging; bile acid; diabetes; energy metabolism; muscle hypertrophy; obesity; skeletal muscle metabolism

Metabolic Syndrome and Cognitive Function in Midlife.

Abstract

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors associated with cognitive decline. We investigated the relationship between MetS and cognition in middle-aged adults. We hypothesized that higher numbers of MetS components will relate to poorer performance on executive function (EF) tasks as frontal lobe regions critical to EF are particularly vulnerable to cardiovascular disease. 197 adults (ages 40-60) participated. MetS was evaluated using established criteria. Composite scores for cognitive domains were computed as follows: Global cognitive function (subtests from the Wechsler Abbreviated Scale of Intelligence, 2nd Edition), EF (Stroop Color Word, Digit Span Backward, and Trails A and B), and memory (California Verbal Learning Test, 2 Edition). Higher number of MetS components was related to weaker EF-F(4, 191) = 3.94, p = .004, MetS components ß = -.14, p = .044. A similar relationship was detected for tests of memory-F(4, 192) = 7.86, p < .001, MetS components ß = -.15, p = .032. Diagnosis of MetS was not significantly associated with EF domain score (ß = -.05, p = .506) but was significantly associated with memory scores-F(4, 189) = 8.81, p < .001, MetS diagnosis ß = -.19, p = .006. Our findings support prior research linking MetS components at midlife to executive dysfunction and demonstrate that MetS, and its components are also associated with poorer memory function. This suggests that cognitive vulnerability can be detected at midlife. Interventions for MetS at midlife could alter cognitive outcomes.

MeSH Terms

-

Keywords

Aging; Brain; Cognitive impairment; Executive function; Metabolic syndrome; Neuropsychological assessment

Interfering Peptides Targeting Protein-Protein Interactions in the Ethylene Plant Hormone Signaling Pathway as Tools to Delay Plant Senescence.

Abstract

Interfering peptides (iPs) have been recognized as valuable substances to specifically target protein-protein interactions (PPIs) in senescence and disease. Although the concept of iPs has been validated for several PPIs in medical and pharmaceutical research, little attention so far has been paid to the enormous potential iPs that may provide to target and control plant growth and developmental processes or plant environmental responses. However, recent research on PPIs in the ethylene signaling pathway has identified the synthetic peptide NOP-1 derived from the nuclear localization signal of ethylene regulator EIN2 as an efficient inhibitor of typical ethylene responses such as ripening, aging, and senescence. Biophysical and biochemical studies on purified recombinant proteins of the ethylene receptor family from various plant species demonstrate that the synthetic peptide binds in the nM-μM range at the plant target. Here, we describe methods to evaluate and quantify the effect of the NOP-1 peptide on flower senescence as a typical ethylene response in the intact plant system. This approach will help to systematically advance our technological capability to delay plant ethylene responses and to expand shelf-life or vase life of fruits and flowers.

MeSH Terms

-

Keywords

Ethylene signaling; Interfering peptides; Plant senescence; Protein–protein interactions

Serum zinc concentrations and characteristics of zinc deficiency/marginal deficiency among Japanese subjects.

Abstract

Studies that have examined serum zinc deficiency/marginal deficiency in developed countries, including Japan, are still limited. The aim of this study was to assess serum zinc concentrations and associated characteristics among Japanese subjects. This cross-sectional study, conducted from September 2016 to December 2018, included 2056 eligible subjects who participated in a voluntary health checkup. Serum zinc concentration categories were defined as deficiency (<60 μg/dL), marginal deficiency (≥60 to <80 μg/dL), and normal (≥80 μg/dL). Serum zinc concentrations were compared between the first age category (<40 years) and other age categories with Dunnett's method. Trends in P-values were estimated using the Jonckheere-Terpstra test for continuous variables. The proportions of subjects with deficiency and marginal deficiency were 0.4% and 46.0% in men, and 0.6% and 38.4% in women, respectively. The deficiency/marginal deficiency group had significantly lower lipid profiles and nutritional status, and a significantly lower proportion were non-daily drinkers in both genders. Older age was significantly associated with lower serum zinc concentration only in men. Our findings clarified a high proportion of serum zinc deficiency/marginal deficiency, especially in men, and suggest a possible association between serum zinc levels and nutritional status and alcohol consumption. It may be necessary to manage nutritional status, including zinc intake.

MeSH Terms

-

Keywords

aging; deficiency; epidemiology; nutrition; prevention; zinc

Essential Amino Acids and Protein Synthesis: Insights into Maximizing the Muscle and Whole-Body Response to Feeding.

Abstract

Ingesting protein-containing supplements and foods provides essential amino acids (EAA) necessary to increase muscle and whole-body protein synthesis (WBPS). Large variations exist in the EAA composition of supplements and foods, ranging from free-form amino acids to whole protein foods. We sought to investigate how changes in peripheral EAA after ingesting various protein and free amino acid formats altered muscle and whole-body protein synthesis. Data were compiled from four previous studies that used primed, constant infusions of L-(ring- H )-phenylalanine and L-(3,3- H )-tyrosine to determine fractional synthetic rate of muscle protein (FSR), WBPS, and circulating EAA concentrations. Stepwise regression indicated that max EAA concentration (EAAC ; R = 0.524, [i]p[/i] < 0.001), EAAC (R = 0.341, [i]p[/i] < 0.001), and change in EAA concentration (ΔEAA; R = 0.345, [i]p[/i] < 0.001) were the strongest predictors for postprandial FSR, Δ (change from post absorptive to postprandial) FSR, and ΔWBPS, respectively. Within our dataset, the stepwise regression equation indicated that a 100% increase in peripheral EAA concentrations increases FSR by ~34%. Further, we observed significant ([i]p[/i] < 0.05) positive (R = 0.420-0.724) correlations between the plasma EAA area under the curve above baseline, EAAC , ΔEAA, and rate to EAAC to postprandial FSR, ΔFSR, and ΔWBPS. Taken together our results indicate that across a large variety of EAA/protein-containing formats and food, large increases in peripheral EAA concentrations are required to drive a robust increase in muscle and whole-body protein synthesis.

MeSH Terms

-

Keywords

aging; amino acid kinetics; anabolism; essential amino acids; muscle protein synthesis; nutrition; protein; protein quality; whole body protein synthesis

Internal Microscopic Diagnosis of Accelerated Aging of Proton Exchange Membrane Water Electrolysis Cell Stack.

Abstract

The hydrogen production reaction of the proton exchange membrane (PEM) water electrolysis cell stack is the reverse reaction of the fuel cell, but the water electrolysis operation requires high pressure, and the high pressure decomposes hydrogen molecules, thus aging or causing failure in the water electrolysis cell stack. In addition, there are five important physical parameters (current, voltage, flow, pressure and temperature) inside the water electrolysis cell stack, which can change the performance and shorten the life of the cell stack. However, the present techniques obtain data only by external simulation or single measurement; they cannot collect the internal real data in operation instantly and accurately. This study discusses the causes for aging or failure, and develops an internal real-time microscopic diagnosis tool for accelerated aging of the PEM water electrolysis cell stack. A flexible integrated (current, voltage, flow, pressure and temperature) microsensor applicable to the inside (high voltage and electrochemical environment) of the PEM water electrolysis cell stack is developed by using micro-electro-mechanical systems (MEMS) technology; it is embedded in the PEM water electrolysis cell stack for microscopic diagnosis of accelerated aging, and 100-h durability and reliability tests are performed. The distribution of important physical parameters inside the PEM water electrolysis cell stack can be measured instantly and accurately, so as to adjust it to the optimal operating conditions, and the local aging and failure problems are discussed.

MeSH Terms

-

Keywords

PEM water electrolysis cell stack; accelerated aging; flexible integrated microsensor; microscopic diagnosis

Influence of aging on deterioration of patients with COVID-19.

Abstract

Aging is an important factor affecting the deterioration of patients with coronavirus disease 2019 (COVID-19). The aging and degeneration of various tissues and organs in the elderly lead to impaired organ function. Underlying conditions such as chronic lung disease, cardiovascular disease, and diabetes in aged patients are associated with higher mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily interacts with the cell surface receptor angiotensin-converting enzyme (ACE) 2 and other accessory proteins such as 78 kDa glucose-regulated protein 78 (GRP78) and CD147. Thus, altered receptor signals in aging and chronic disease play a role in SARS-CoV-2 infection, and are associated with a higher risk of deterioration in different organs. In this review, after a brief introduction to the link between aging and receptors for SARS-CoV-2, we focus on the risk of deterioration in different organs of COVID-19 patients considering aging as the main factor. We further discuss the structural and/or physiological changes in the immune system and organs (lung, heart, kidney, vessels, nerve system), as well as those associated with diabetes, in aging patients, and speculate on the most likely mechanisms underlying the deterioration of COVID-19 patients.

MeSH Terms

-

Keywords

ACE2; CD147; COVID-19; GRP78; aging

Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys.

Abstract

Cortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury and can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles (MSC-EVs), administered intravenously at both 24 h and 14 days after cortical injury reduced microgliosis (Go et al. 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of treatment with MSC-EVs on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle-treated control, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively-myelinating oligodendrocytes in in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and likely improve functional recovery after injury in the aged brain. SIGNIFICANCE: We previously reported that after cortical injury in the aged monkey brain, EVs reduce neuronal pathology (Medalla et al. 2020), microgliosis (Go et al. 2019), and facilitate recovery of function. However, the effect of injury on oligodendrocytes and myelination has not been characterized in the primate brain (Dewar et al. 1999; Sozmen et al. 2012; Zhang et al. 2013). In the present study, we assessed changes in myelination after cortical injury in these same aged monkeys. Our results show, for the first time, that MSC-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain.

MeSH Terms

-

Keywords

Aging; Cortical injury; Extracellular vesicles; Monkeys; Myelin; Non-human primates; Oligodendrocytes; Stroke; White matter

Skin Viral Infections: Host Antiviral Innate Immunity and Viral Immune Evasion.

Abstract

The skin is an active immune organ that functions as the first and largest site of defense to the outside environment. Serving as the primary interface between host and pathogen, the skin's early immune responses to viral invaders often determine the course and severity of infection. We review the current literature pertaining to the mechanisms of cutaneous viral invasion for classical skin-tropic, oncogenic, and vector-borne skin viruses. We discuss the skin's evolved mechanisms for innate immune viral defense against these invading pathogens, as well as unique strategies utilized by the viruses to escape immune detection. We additionally explore the roles that demographic and environmental factors, such as age, biological sex, and the cutaneous microbiome, play in altering the host immune response to viral threats.

MeSH Terms

-

Keywords

antiviral proteins; cutaneous innate immunity; cutaneous microbiome; skin aging; skin antiviral response; skin viruses

Sequenced application of glutathione as an antioxidant with an organic biostimulant improves physiological and metabolic adaptation to salinity in wheat.

Abstract

Globally, salinity threatens the agricultural crops productivity by inhibiting plant growth and development through osmotic stress and ionic cytotoxicity. The polygenic nature of salinity offers several pragmatic shotgun approaches to improve salinity tolerance. The present study investigated the potential of glutathione (GSH; 1 mM) as an antioxidant and moringa leaf extract (MLE; 3%) as an organic biostimulant applied in sequence as seed priming and foliar spray on wheat growth, physiology and metabolic adaptation under saline conditions (9.16 dS m ). Plants without any treatment and water spray (H O) were considered controls. Salinity induced osmotic stress reduced the plant tissue water status and photosynthetic performance, and perturbed ionic (K /Na , Ca /Na , K +Ca /Na ) and hormonal (IAA, GA , zeatin, ABA) homeostasis, consequently affected growth and yield in wheat. Sequenced applied MLE and/or GSH improved osmotic stress tolerance by stabilizing membrane integrity and decreasing electrolyte leakage. These positive results were owed to enhanced endogenous GSH and ascorbate levels. Improved tissue water status was attributed to increased osmotic adjustment, better ionic and hormonal homeostasis contributed to improving photosynthetic efficiency and growth under salinity. Exogenously applied MLE and GSH sequences improved grain yield, which was attributed to the maintenance of green leaf area and delayed senescence associated with an increase in photosynthetic pigments and chlorophyll fluorescence traits. In crux, exogenous applied MLE and/or GSH can be the best physiological strategy to reduce the deleterious effects of salinity and improve physiological and metabolic adaptation in wheat under saline field conditions.

MeSH Terms

-

Keywords

Antioxidants; Delayed senescence; Ionic homeostasis; Osmotic stress; Photosynthetic efficiency

Carnitine promotes recovery from oxidative stress and extends lifespan in [i]C. elegans[/i].

Abstract

Carnitine is required for transporting fatty acids into the mitochondria for β-oxidation. Carnitine has been used as an energy supplement but the roles in improving health and delaying aging remain unclear. Here we show in [i]C. elegans[/i] that L-carnitine improves recovery from oxidative stress and extends lifespan. L-carnitine promotes recovery from oxidative stress induced by paraquat or juglone and improves mobility and survival in response to H O and human amyloid (Aβ) toxicity. L-carnitine also alleviates the oxidative stress during aging, resulting in moderate but significant lifespan extension, which was dependent on SKN-1 and DAF-16. Long-lived worms with germline loss ([i]glp-1[/i]) or reduced insulin receptor activity ([i]daf-2)[/i] recover from aging-associated oxidative stress faster than wild-type controls and their long lifespans were not further increased by L-carnitine. A new gene, T08B1.1, aligned to a known carnitine transporter OCTN1 in humans, is required for L-carnitine uptake in [i]C. elegans[/i]. T08B1.1 expression is elevated in [i]daf-2[/i] and [i]glp-1[/i] mutants and its knockdown prevents L-carnitine from improving oxidative stress recovery and prolonging lifespan. Together, our study suggests an important role of L-carnitine in oxidative stress recovery that might be important for healthy aging in humans.

MeSH Terms

-

Keywords

aging; amyloid; carnitine; oxidative stress; transporter

Effects of Matcha Green Tea Powder on Cognitive Functions of Community-Dwelling Elderly Individuals.

Abstract

Matcha Green Tea Powder contains a variety of active ingredients beneficial to health, such as tea catechins, lutein and vitamin K. It is also known that these ingredients confer benefits upon cognitive functions of elderly people. Therefore, we aimed to investigate the relationship between a daily supplementation of Matcha and the change in cognitive functions of community-dwelling elderly people. A randomized, double-blind, placebo-controlled 12-week trial was performed. Sixty-one participants were recruited and randomly assigned to receive test drink containing 3g powder from fresh Matcha or placebo powder per day. Changes in cognitive function were assessed utilizing a psychometric test battery. Daily food intake was assessed by a Brief-type Self-administered Diet History Questionnaire (BDHQ). In the gender-specific analysis, a significant cognitive enhancement was observed in the Montreal Cognitive Assessment (MoCA) score in the active group of women. In dietary analysis, we found a significant inverse correlation between consumption of vitamin K in daily diet, excluding test drinks, and change in MoCA. The present study suggests that daily supplementation of Matcha Green Tea Powder has protective effects against cognitive decline in community-dwelling elderly women.

MeSH Terms

-

Keywords

aging; cognitive function; green tea; impulsivity; memory function; vitamin K

Heterozygous disruption of ALAS1 in mice causes an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver.

Abstract

5-Aminolevulinic acid (ALA) is the rate-limiting intermediate in heme biosynthesis in vertebrate species; a reaction catalyzed by the mitochondrial ALA synthase 1 (ALAS1) enzyme. Previously we reported that knockdown of the ubiquitously expressed ALAS1 gene in mice disrupts normal glucose metabolism, attenuates mitochondrial function and results in a prediabetic like phenotype when animals pass 20-weeks of age (Saitoh et al., 2018). Contrary to our expectations, the cytosolic and mitochondrial heme content of ALAS1 heterozygous (A1+/-) mice were similar to WT animals. Therefore, we speculated that regulatory "free heme" may be reduced in an age dependent manner in A1 ± mice, but not total heme. Here, we examine free and total heme from the skeletal muscle and liver of WT and A1 ± mice using a modified acetone extraction method and examine the effects of aging on free heme by comparing the amounts at 8-12 weeks and 30-36 weeks of age, in addition to the mRNA abundance of ALAS1. We found an age-dependent reduction in free heme in the skeletal muscle and liver of A1 ± mice, while WT mice showed only a slight decrease in the liver. Total heme levels showed no significant difference between young and aged WT and A1 ± mice. ALAS1 mRNA levels showed an age-dependent reduction similar to that of free heme levels, indicating that ALAS1 mRNA expression levels are a major determinant for free heme levels. The free heme pools in skeletal muscle tissue were almost 2-fold larger than that of liver tissue, suggesting that the heme pool varies across different tissue types. The expression of heme oxygenase 1 (HO-1) mRNA, which is expressed proportionally to the amount of free heme, were similar to those of free heme levels. Taken together, this study demonstrates that the free heme pool differs across tissues, and that an age-dependent reduction in free heme levels is accelerated in mice heterozygous for ALAS1, which could account for the prediabetic phenotype and mitochondrial abnormality observed in these animals.

MeSH Terms

-

Keywords

5-Aminolevulinate synthase 1 (ALAS1); 5-Aminolevulinic acid (ALA); Aging; Free heme; Liver; Skeletal muscle

Effects of exercise-heat stress on circulating stress hormones and interleukin-6 in young and older men.

Abstract

Aging is associated with impairments in thermoregulatory function, which may augment the neuroendocrine and immune response in older relative to young adults during physical activity in the heat. This study was therefore aimed at examining changes in circulating endocrine hormones as cortisol (COR), prolactin (PRL), human growth hormone (hGH) and interleukin-6 (IL-6) in young and older men prior to and following an incremental, exercise-heat stress protocol (40°C and ~15% relative humidity). Accordingly, ten habitually active young (mean±SD; 21 ± 1 years) and ten older (65 ± 3 years) men performed three 30-min bouts of cycling at increasing metabolic heat productions (300, 400 and 500 W, equal to light, moderate and vigorous exercise), each separated by a 15-min recovery. Consistent with our hypothesis, we observed augmented IL-6 in older (3.55 ± 1.62 pg/mL) compared to young men (1.59 ± 0.88 pg/mL) following the protocol (p < 0.001). However, no significant between-group differences were observed for COR and hGH (all p > 0.050). We show that when assessed following incremental exercise in the heat, older men display augmented interleukin-6, but similar levels of stress hormones relative to young men.

MeSH Terms

-

Keywords

Heat stress; aging; core temperature; immune; stress; stress hormones

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

Abstract

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

MeSH Terms

-

Keywords

aging; atrophy; cortex; sleep

GATA6 regulates aging of human mesenchymal stem/stromal cells.

Abstract

Cellular reprogramming forcing the expression of pluripotency markers can reverse aging of cells but how molecular mechanisms through which reprogrammed cells alter aging-related cellular activities still remain largely unclear. In this study, we reprogrammed human synovial fluid-derived mesenchymal stem cells (MSCs) into induced pluripotent stem cells (iPSCs) using six reprogramming factors and reverted the iPSCs back to MSCs, as an approach to cell rejuvenation. Using the parental and reprogrammed MSCs as control nonrejuvenated and rejuvenated cells, respectively, for comparative analysis, we found that aging-related activities were greatly reduced in reprogrammed MSCs compared with those in their parental lines, indicating reversal of cell aging. Global transcriptome analysis revealed differences in activities of regulatory networks associated with inflammation and proliferation. Mechanistically, we demonstrated that, compared with control cells, the expression of GATA binding protein 6 (GATA6) in reprogrammed cells was attenuated, resulting in an increase in the activity of sonic hedgehog signaling and the expression level of downstream forkhead box P1 (FOXP1), in turn ameliorating cellular hallmarks of aging. Lower levels of GATA6 expression were also found in cells harvested from younger mice or lower passage cultures. Our findings suggest that GATA6 is a critical regulator increased in aged MSCs that controls the downstream sonic hedgehog signaling and FOXP1 pathway to modulate cellular senescence and aging-related activities.

MeSH Terms

-

Keywords

aging; cell signaling; mesenchymal stem cells; reprogramming; transcription factors

The Aging Stress Response and Its Implication for AMD Pathogenesis.

Abstract

Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5'AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1. Peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1α), encoded by the [i]PPARGC1A[/i] gene, playing an important role in antioxidant defense and mitochondrial biogenesis, may interact with these molecules influencing lifespan and general fitness. Perturbation in the aging stress response may lead to aging-related disorders, including age-related macular degeneration (AMD), the main reason for vision loss in the elderly. This is supported by studies showing an important role of disturbances in mitochondrial metabolism, DDR and autophagy in AMD pathogenesis. In addition, disturbed expression of PGC-1α was shown to associate with AMD. Therefore, the aging stress response may be critical for AMD pathogenesis, and further studies are needed to precisely determine mechanisms underlying its role in AMD. These studies can include research on retinal cells produced from pluripotent stem cells obtained from AMD donors with the mutations, either native or engineered, in the critical genes for the aging stress response, including [i]AMPK[/i], [i]IGF1[/i], [i]MTOR[/i], [i]SIRT1[/i] and [i]PPARGC1A[/i].

MeSH Terms

-

Keywords

AMD; DNA damage response; PGC-1α; SIRT1; age-related macular degeneration; aging; autophagy; insulin/IGF-1; mitochondrial quality control; the aging stress response

The Impact of Age on the Association Between Physical Activity and White Matter Integrity in Cognitively Healthy Older Adults.

Abstract

Cognition emerges from coordinated processing among distributed cortical brain regions, enabled through interconnected white matter networks. Cortical disconnection caused by age-related decline in white matter integrity (WMI) is likely to contribute to age-related cognitive decline. Physical activity (PA) has been suggested to have beneficial effects on white matter structure. However, its potential to counteract age-related decline in WMI is not yet well established. The present explorative study analyzed if PA was associated with WMI in cognitively healthy older adults and if this association was modulated by age. Forty-four cognitively healthy older individuals (aged 60-88 years) with diffusion-tensor imaging (DTI) and PA measurements were included from the AgeGain study. Voxelwise analysis using Tract-Based Spatial Statistics (TBSS) demonstrated that PA was associated with WMI in older adults. However, results emphasized that this association was restricted to high age. The association between PA and WMI was found in widespread white matter regions suggesting a global rather than a regional effect. Supplementary analyses demonstrated an association between the integrity of these regions and the performance in memory [verbal learning and memory test (VLMT)] and executive functioning (Tower of London).Results of the present explorative study support the assumption that PA is associated with WMI in older adults. However, results emphasize that this association is restricted to high age. Since cognitive decline in the elderly is typically most pronounced in later stages of aging, PA qualifies as a promising tool to foster resilience against age-related cognitive decline, [i]via[/i] the preservation of the integrity of the brains WM.

MeSH Terms

-

Keywords

actigraphy; cognition; healthy aging; physical activity; white matter integrity

Childhood adversity and trajectories of multimorbidity in mid-late life: China health and longitudinal retirement study.

Abstract

The association between childhood adversity and an individual's health in later life has been extensively studied in Western societies; however, little is known about this association for the development of multimorbidity in China. Three waves (2011-2012, 2013 and 2015) of the China Health and Retirement Longitudinal Study were used for adults aged 45-101 years. Multimorbidity was assessed by the summed scores of self-reported physician diagnoses of 14 chronic diseases. Childhood adversity was measured by the incidence of childhood abuse and neglect, negative caregiver's characteristics and low socioeconomic status. Latent growth curve modelling was used to investigate the trajectory of multimorbidity by childhood adversity. Parental physical abuse was associated with increased number of chronic diseases (intercept: 0.119; 95% CI: 0.033 to 0.205 for men and 0.268: 95% CI: 0.188 to 0.348 for women) and a higher rate of increase (slope: 0.013: 95% CI: 0.000 to 0.027 for men and 0.022: 95% CI: 0.008 to 0.036 for women) in multimorbidity. Adequacy of food was associated with a lower number chronic diseases at baseline (men: -0.171: 95% CI: -0.245 to -0.097; women: -0.223: 95% CI: -0.294 to -0.152) and a slower rate of change in multimorbidity (men: -0.015 per year: 95% CI: -0.027 to -0.003; women: -0.012 per year: 95% CI: -0.024 to -0.001). The results demonstrate that childhood adversity exerts long-lasting effects on multimorbidity among older adults in China. Prevention of childhood maltreatment may delay or even avert the emergence of multimorbidity in later life.

MeSH Terms

-

Keywords

gerontology; life course epidemiology; lifecourse / childhood circumstances; morbidity; social and life-course epidemiology

Acute effects of inspiratory loading in older women: Where the breath meets the heart.

Abstract

We tested the hypothesis that inspiratory resistive loading (IRL) increases vagal-mediated complexity of heart rate variability (HRV) in older women. We recorded heart rate continually during 30 breaths with Sham or IRL (30 % of maximal inspiratory pressure) in sitting position. The normalized spectral power in the low (LFn) and high (HFn) frequency bands and the symbolic dynamics measures for 0 V, 2UV and 2 L V were obtained. HFn was higher and LFn was lower during IRL than Sham (p < 0.05). During IRL, 2UV component increased more than Sham (p < 0.05) while 0 V index remained unchanged (p> 0.05). In conclusion, acute IRL improved vagal modulation index of both linear (spectral analysis) and non-linear analysis (symbolic dynamics) in older women.

MeSH Terms

-

Keywords

Aging; Heart rate variability; Maximal inspiratory pressure; Respiratory muscles

[Aryl hydrocarbon receptor interacting protein (AIP) in human dermis during aging.]

Abstract

The aim of this work was to examine the content of aryl hydrocarbon receptor interacting protein (AIP) in fibroblasts of human dermis from 20 weeks of pregnancy until 85 years old, and defining of a role of AIP in age-dependent changes in the number of fibroblasts in the dermis. AIP, proliferating cells nuclear antigen (PCNA) were detected with indirect immunohistochemical technique. Results showed that a portion of fibroblasts with positive staining for AIP in the dermis is gradually increased from 20 weeks of pregnancy until 85 years old. A total number and percent of PCNA positive fibroblasts in dermis decreased with progression of age. Most sufficient age-dependent reduction in a total and PCNA positive number of dermal fibroblast was observed from antenatal until 40 years of life. Correlation analysis showed that both age-dependent decrease in the number of fibroblasts and retardation of their proliferation are significantly associated with age-related increase in the number of AIP positive fibroblasts in dermis. Results allow to suggest that AIP is involved in age-dependent decrease in the number and proliferation of fibroblasts in human dermis.

MeSH Terms

-

Keywords

AIP; PCNA; aging; fibroblasts; skin

Evaluation of latent fingermark color contrast as aging parameter under different environmental conditions: A preliminary study.

Abstract

This research expands previous studies in which color contrast between ridges and furrows of powder-enhanced latent fingermarks was explored as a possible aging parameter. The main goal is to test the sensitivity of the technique across a predetermined set of factors. In this case, experiment factors have included two donors who deposited sebaceous- and eccrine-rich fingermarks onto ceramic tile and polystyrene plastic. These were developed with either black carbon or titanium dioxide powder (TiO ) over eight time periods (0-72 days) and aged under three light conditions (direct light, shade, and darkness). The mean intensity (MI) and intensity amplitude (IA) metrics of color were collected from each image for statistical analyses. Results show that color contrast is affected significantly by substrate, secretion, and powder types, with an interaction effect between the substrate and powder type on both MI and IA metrics. The degree of light exposure did not have a noticeable impact on distinguishing aging patterns of fingermarks by neither powder methods. Different aging patterns were detected between sebaceous-rich and their eccrine-rich counterparts for all light conditions using regression analysis. All eccrine-rich fingermarks exhibited little (or minimal) change in IA over time, whereas sebaceous-rich samples showed varied patterns, from significant decreases to slight increases. These findings confirm and expand previous observations on the potential use of MI and IA as metrics to study latent fingermark degradation patterns that could eventually be used to estimate the age of a fingermark.

MeSH Terms

-

Keywords

aging; carbon black; color contrast; degradation; environment; fingerprint; latent fingermark; powder; titanium dioxide

Altered heart rate variability during sleep in mild cognitive impairment.

Abstract

Cardiovascular autonomic dysfunction, as measured by short-term diurnal heart rate variability (HRV), has been reported in older adults with mild cognitive impairment (MCI). However, it is unclear whether this impairment also exists during sleep in this group. We, therefore, compared overnight HRV during sleep in older adults with MCI and those with subjective cognitive impairment (SCI). Older adults (n = 210) underwent overnight polysomnography. Eligible participants were characterized as multi-domain MCI or SCI. The multi-domain MCI group was comprised of amnestic and non-amnestic subtypes. Power spectral analysis of HRV was conducted on the overnight electrocardiogram during non-rapid eye movement (NREM), rapid eye movement (REM), N1, N2, N3 sleep stages, and wake periods. High-frequency HRV (HF-HRV) was employed as the primary measure to estimate parasympathetic function. The MCI group showed reduced HF-HRV during NREM sleep (p = 0.018), but not during wake or REM sleep (p > 0.05) compared to the SCI group. Participants with aMCI compared to SCI had the most pronounced reduction in HF-HRV across all NREM sleep stages-N1, N2, and N3, but not during wake or REM sleep. The naMCI sub-group did not show any significant differences in HF-HRV during any sleep stage compared to SCI. Our study showed that amnestic MCI participants had greater reductions in HF-HRV during NREM sleep, relative to those with SCI, suggesting potential vulnerability to sleep-related parasympathetic dysfunction. HF-HRV, especially during NREM sleep, may be an early biomarker for dementia detection.

MeSH Terms

-

Keywords

aging; dementia; heart rate variability; mild cognitive impairment; sleep

Melatonin delays leaf senescence of postharvest Chinese flowering cabbage through ROS homeostasis.

Abstract

Reactive oxygen species (ROS) trigger and accelerate leaf senescence. Melatonin, a low molecular compound with several biological functions in plants, is known to delay leaf senescence in different species, including Chinese flowering cabbage. However, the mechanism(s) underpinning melatonin-delayed leaf senescence remains unclear. Here, we found that melatonin lowered the expression of chlorophyll catabolic genes (BrPAO and BrSGR1) and senescence-associated genes (BrSAG12 and BrSEN4), decreased chlorophyll loss, minimized the alteration in Fv/Fm ratio and remarkably delayed senescence of Chinese flowering cabbage after harvest. Moreover, the over-accumulation of O , hydrogen peroxide (H O ) and malondialdehyde contents and the expression of respiratory burst oxidase homologues (RBOH) genes (BrRbohB, BrRbohC, BrRbohD, BrRbohD2 and BrRbohE) were significantly inhibited by melatonin treatment. Melatonin-treated cabbages also showed higher O , OH and DPPH radical scavenging capacity and enhanced activities of peroxidase (POD), superoxide dismutase (SOD) and their gene expressions. Up-regulation of key components of ascorbate-glutathione (AsA-GSH) cycle, the metabolic pathway that detoxify H O , was also observed in melatonin-treated cabbages. These findings suggest that melatonin-delayed postharvest leaf senescence of postharvest Chinese flowering cabbage may be mediated, at least in part, by maintaining ROS homeostasis through restraining RBOHs-catalyzed ROS production and enhancing the activity of ROS-scavenging system including major antioxidant enzymes and AsA-GSH cycle.

MeSH Terms

-

Keywords

Chinese flowering cabbage; Leaf senescence; Melatonin; ROS homeostasis

Smart Nanofibers with Natural Extracts Prevent Senescence Patterning in a Dynamic Cell Culture Model of Human Skin.

Abstract

Natural cosmetic products have recently re-emerged as a novel tool able to counteract skin aging and skin related damages. In addition, recently achieved progress in nanomedicine opens a novel approach yielding from combination of modern nanotechnology with traditional treatment for innovative pharmacotherapeutics. In the present study, we investigated the antiaging effect of a pretreatment with [i]Myrtus communis[/i] natural extract combined with a polycaprolactone nanofibrous scaffold (NanoPCL-M) on skin cell populations exposed to UV. We set up a novel model of skin on a bioreactor mimicking a crosstalk between keratinocytes, stem cells and fibroblasts, as in skin. Beta-galactosidase assay, indicating the amount of senescent cells, and viability assay, revealed that fibroblasts and stem cells pretreated with NanoPCL-M and then exposed to UV are superimposable to control cells, untreated and unexposed to UV damage. On the other hand, cells only exposed to UV stress, without NanoPCL-M pretreatment, exhibited a significantly higher yield of senescent elements. Keratinocyte-based 3D structures appeared disjointed after UV-stress, as compared to NanoPCL-M pretreated samples. Gene expression analysis performed on different senescence associated genes, revealed the activation of a molecular program of rejuvenation in stem cells pretreated with NanoPCL-M and then exposed to UV. Altogether, our results highlight a future translational application of NanoPCL-M to prevent skin aging.

MeSH Terms

-

Keywords

4D dynamic model; biophysics; cell senescence; cellular mechanisms; nanofibers; natural extracts; precision medicine; skin aging; stem cells

Do TUNEL and Other Apoptosis Assays Detect Cell Death in Preclinical Studies?

Abstract

The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay detects DNA breakage by labeling the free 3'-hydroxyl termini. Given that genomic DNA breaks arise during early and late stages of apoptosis, TUNEL staining continues to be widely used as a measure of apoptotic cell death. The advantages of the assay include its relative ease of performance and the broad availability of TUNEL assay kits for various applications, such as single-cell analysis of apoptosis in cell cultures and tissue samples. However, as briefly discussed herein, aside from some concerns relating to the specificity of the TUNEL assay itself, it was demonstrated some twenty years ago that the early stages of apoptosis, detected by TUNEL, can be reversed. More recently, compelling evidence from different biological systems has revealed that cells can recover from even late stage apoptosis through a process called anastasis. Specifically, such recovery has been observed in cells exhibiting caspase activation, genomic DNA breakage, phosphatidylserine externalization, and formation of apoptotic bodies. Furthermore, there is solid evidence demonstrating that apoptotic cells can promote neighboring tumor cell repopulation (e.g., through caspase-3-mediated secretion of prostaglandin E ) and confer resistance to anticancer therapy. Accordingly, caution should be exercised in the interpretation of results obtained by the TUNEL and other apoptosis assays (e.g., caspase activation) in terms of apoptotic cell demise.

MeSH Terms

-

Keywords

DNA strand breakage; TUNEL; anastasis; apoptosis; cancer therapy; micronucleation; polyploid giant cancer cells; reversal; senescence

Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging.

Abstract

Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

MeSH Terms

-

Keywords

Aging brain; CSF; CSF dynamics; CSF elimination rate constants; CSF outflow; Dural CSF drainage; Interstitial fluid (ISF); Nasal/across the cribriform plate CSF drainage; Spinal nerves CSF drainage

Motility in Frail Older Adults: Operationalization of a New Framework and First Insights into Its Relationship with Physical Activity and Life-Space Mobility: An Exploratory Study.

Abstract

In order to design effective interventions to prevent age-related mobility loss, it is important to identify influencing factors. The concept of "motility" by Kaufmann et al. subdivides such factors into three categories: "access", "skills", and "appropriation". The aim of this study was to assemble appropriate quantitative assessment tools for the assessment of these factors in frail older adults and to get first insights into their relative contribution for life-space and physical activity-related mobility. This is an exploratory cross-sectional study conducted with twenty-eight at least prefrail, retired participants aged 61-94. Life-space mobility was assessed using the "University of Alabama at Birmingham Life-space Assessment" (LSA) and physical activity using the "German Physical Activity Questionnaire" (PAQ50+). Factors from the category "appropriation", followed by factors from the category "skills" showed the strongest associations with the LSA. Factors from the category "access" best explained the variance for PAQ50+. This study's findings indicate the importance of accounting for and examining comprehensive models of mobility. The proposed assessment tools need to be explored in more depth in longitudinal studies with larger sample sizes in order to yield more conclusive results about the appropriateness of the motility concept for such purposes.

MeSH Terms

-

Keywords

aging; frailty; life-space assessment; mobility determinants

Cognitive reserve relates to executive functioning in the old-old.

Abstract

Cognitive reserve (CR) is known to reduce or even protect against the negative effects of aging on cognitive functioning. Nonetheless, little is known about how CR influences the relationship between different cognitive abilities and age in the old-old. The goal of the present study was, therefore, to test the hypothesis whether, in the old-old, CR still modifies the relationship between age and cognitive functioning. Eighty-three adults (aged 71-94) without mild cognitive impairment or dementia residing in residential care facilities completed a detailed neuropsychological test battery. CR was estimated using a combination of educational attainment and an estimation of verbal intelligence. Moderation analyses revealed a significant effect for fluency and a trend for flexibility, showing that the negative relationship between age and cognitive performance is reduced as the level of CR increases. These results demonstrate that CR still influences the relationship between age and executive functions in adults of advanced age.

MeSH Terms

-

Keywords

Aging; Cognitive reserve; Episodic memory; Executive functions; Information processing speed

Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2 mice.

Abstract

Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradation via mitophagy to maintain energy homeostasis. We hypothesize that LRRK2 (leucine-rich repeat kinase 2) mutation disrupts mitochondrial turnover causing accumulation of defective mitochondria in aging brain. We found more ubiquitinated mitochondria with aberrant morphology associated with impaired function in aged (but not young) LRRK2 knockin mutant mouse striatum compared to wild-type (WT) controls. LRRK2 mutant mouse embryonic fibroblasts (MEFs) exhibited reduced MAP1LC3/LC3 activation indicating impaired macroautophagy/autophagy. Mutant MEFs under FCCP-induced (mitochondrial uncoupler) stress showed increased LC3-aggregates demonstrating impaired mitophagy. Using a novel flow cytometry assay to quantify mitophagic rates in MEFs expressing photoactivatable [i]mito[/i]-PAmCherry, we found significantly slower mitochondria clearance in mutant cells. Specific LRRK2 kinase inhibition using GNE-7915 did not alleviate impaired mitochondrial clearance suggesting a lack of direct relationship to increased kinase activity alone. DNM1L/Drp1 knockdown in MEFs slowed mitochondrial clearance indicating that DNM1L is a prerequisite for mitophagy. DNM1L knockdown in slowing mitochondrial clearance was less pronounced in mutant MEFs, indicating preexisting impaired DNM1L activation. DNM1L knockdown disrupted mitochondrial network which was more evident in mutant MEFs. DNM1L-Ser616 and MAPK/ERK phosphorylation which mediate mitochondrial fission and downstream mitophagic processes was apparent in WT using FCCP-induced stress but not mutant MEFs, despite similar total MAPK/ERK and DNM1L levels. In conclusion, aberrant mitochondria morphology and dysfunction associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in mutant LRRK2 MEFs and mouse brain. ATP: adenosine triphosphate; BAX: BCL2-associated X protein; CDK1: cyclin-dependent kinase 1; CDK5: cyclin-dependent kinase 5; CQ: chloroquine; CSF: cerebrospinal fluid; DNM1L/DRP1: dynamin 1-like; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell sorting; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; LAMP2A: lysosomal-associated membrane protein 2A; LRRK2: leucine-rich repeat kinase 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK1/ERK2: mitogen-activated protein kinase 1; MEF: mouse embryonic fibroblast; MFN1: mitofusin 1; MMP: mitochondrial membrane potential; PAmCherry: photoactivatable-mCherry; PD: Parkinson disease; PINK1: PTEN induced putative kinase 1; PRKN/PARKIN: parkin RBR E3 ubiquitin protein ligase; RAB10: RAB10, member RAS oncogene family; RAF: v-raf-leukemia oncogene; SNCA: synuclein, alpha; TEM: transmission electron microscopy; VDAC: voltage-dependent anion channel; WT: wild type; SQSTM1/p62: sequestosome 1.

MeSH Terms

-

Keywords

Aging; Dnm1l/DRP1; SQSTM1/p62; knockin mice; macroautophagy; mitochondria dysfunction; mitochondrial fission; mitophagy; parkinson disease; ubiquitination

An Updated Review: Androgens and Cognitive Impairment in Older Men.

Abstract

Androgens are some of the most important sex hormones in men, and they maintain important physiological activities in the human body. Cognitive impairment is one of the most common manifestations of aging in the elderly population and an important factor affecting the quality of life of elderly individuals. The levels of sex hormones in elderly people decrease with age, and low levels of androgens in older male individuals have been closely linked to the development of cognitive impairment. Basic studies have shown that androgens have neuroprotective effects and that androgen deficiency impairs cognitive function by increasing oxidative stress and decreasing synaptic plasticity, among other effects. Additionally, clinical studies have also shown that androgen deficiency is closely related to cognitive impairment. This article reviews the relationship between low androgen levels and cognitive impairment, their potential mechanisms, and the effects of testosterone supplementation in improving cognition.

MeSH Terms

-

Keywords

aging; androgen; cognitive impairment; molecular mechanism; older men

The Prevalence of Sarcopenic Obesity in Postmenopausal Women with a History of Breast Cancer Depending on Adopted Methodology - A Case-Control Study.

Abstract

Sarcopenic obesity (SO) is characterized as the cooccurrence of sarcopenia and obesity. It is associated with many adverse health consequences, also in oncological patients. The study aimed to assess the prevalence of SO in postmenopausal women with a history of breast cancer depending on adopted methodology. The case-control study enrolled 103 women over the age of 50 with a history of breast cancer, including women who completed oncological treatment and had remained in remission for at least 5 years (group I, n=78) and women in whom the disease recurred (group II, n=25). The control group included women with no history of breast cancer (group III, n=73). In group II sarcopenia occurred significantly more commonly compared to both group I and the control group (for the skeletal muscle index (SMI) ≤29.20%: 13 (52%) in group II vs 16 (20.5%) in group I, p=0.004 and 3 (4.1%) in group III, p<0.001; for SMI ≤26.60%: 10 (40%) in group II vs 9 (11.5%) in group I, p=0.003 and 3 (4.1%) in group III, p<0.001; for SMI ≤33.87%: 17 (68%) in group II vs 21 (26.9%) in group I, p<0.001 and 5 (6.8%) in group III, p<0.001). Depending on the assessment criteria, SO was diagnosed in 0-11.5% of cases in group I, 0-40% of cases in group II and 0-4.1% in the control group. Intergroup differences were not statistically significant, irrespective of the adopted pair of diagnostic criteria. The highest detectability of SO was observed when SMI was combined with each of the diagnostic criteria for obesity used. SO diagnosis based on the percentage of fatty tissue mass in the body of >38% and SMI value were associated with a higher detection rate of SO in each study group, regardless of the adopted cut-off value. Similar results were obtained in each analyzed group when using the remaining diagnostic criteria for obesity and SMI value, regardless of the cut-off value.

MeSH Terms

-

Keywords

aging; breast neoplasms; menopause; muscles; obesity; sarcopenia

Association of [i]APOE[/i] E2 and low-density lipoprotein with depressive symptoms in Chinese senile schizophrenia inpatients: A cross-sectional study.

Abstract

Schizophrenia is considered to occur due to both environmental and genetic factors. Depressive symptoms and apolipoprotein E ([i]APOE[/i]) gene polymorphisms are involved in the pathogenesis of schizophrenia. However, the effect of [i]APOE[/i] gene polymorphism on depressive symptoms has never been investigated among Chinese elderly schizophrenia patients. This cross-sectional study aimed to determine the effect of [i]APOE[/i] gene polymorphism on blood lipid metabolism and depressive symptoms among elderly schizophrenia patients. A total of 301 elderly schizophrenia patients (161 males, age ranges from 60 to 92 years, with an average age of 67.31 ± 6.667) were included in the study. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). [i]APOE[/i] gene polymorphisms were determined by polymerase chain reaction (PCR). Correlations between GDS and serum low-density lipoprotein (LDL) levels with [i]APOE[/i] genotypes were assessed. The concentration of LDL in the [i]APOE[/i] E2 group was significantly lower than those in the [i]APOE[/i] E3 and [i]APOE[/i] E4 groups, and the GDS scores in the [i]APOE[/i] E2 and [i]APOE[/i] E3 groups were higher than those in the [i]APOE[/i] E4 group. Using partial correlation analysis and controlling the duration of disease and hyperlipidemia, we found that GDS scores were significantly correlated with LDL ([i]r[/i] = -0.179, [i]p[/i] = 0.025). [i]The APOE[/i] E2 genotype is associated with more depressive symptoms and lower serum LDL in elderly Chinese schizophrenia patients, and there is a negative correlation between depressive symptoms and LDL.

MeSH Terms

-

Keywords

APOE; Aging; Chinese; Depressive symptoms; Schizophrenia

Interaction of Age and Self-reported Physical Sports Activity on White Matter Hyperintensity Volume in Healthy Older Adults.

Abstract

Cerebral white matter (WM) lesion load, as measured by white matter hyperintensity (WMH) volume with magnetic resonance imaging (MRI), has been associated with increasing age and cardiovascular risk factors, like hypertension. Physical sports activity (PSA) may play an important role in maintaining WM in the context of healthy aging. In 196 healthy older adults, we investigated whether participants reporting high levels of PSA ([i]n[/i] = 36) had reduced total and regional WMH volumes compared to those reporting low levels of PSA ([i]n[/i] = 160). Age group [young-old (YO) = 50-69 years; old-old (OO) = 70-89 years], PSA group, and age by PSA group interaction effects were tested, with sex, hypertension, and body mass index (BMI) as covariates. We found significant main effects for age group and age by PSA group interactions for total, frontal, temporal, and parietal WMH volumes. There were no main effects of PSA group on WMH volumes. The OO group with low PSA had greater total, frontal, temporal, and parietal WMH volumes than the YO with low PSA and OO with high PSA groups. WMH volumes for the YO and OO groups with high PSA were comparable. These findings indicate an age group difference in those with low PSA, with greater WMH volumes in older adults, which was not observed in those with high PSA. The results suggest that engaging in high levels of PSA may be an important lifestyle factor that can help to diminish WMH lesion load in old age, potentially reducing the impact of brain aging.

MeSH Terms

-

Keywords

MRI; healthy aging; moderate to vigorous physical activity (MVPA); physical activity (exercise); regional white matter lesion load; white matter (WM); white matter hyperintensity volume

Mapping and understanding the decision-making process for providing nutrition and hydration to people living with dementia: a systematic review.

Abstract

This systematic review aimed to explore the process of decision-making for nutrition and hydration for people living with dementia from the perspectives and experiences of all involved. We searched CINAHL, the Cochrane Library, EMBASE, MEDLINE and PsycINFO databases. Search terms were related to dementia, decision-making, nutrition and hydration. Qualitative, quantitative and case studies that focused on decision-making about nutrition and hydration for people living with dementia were included. The CASP and Murad tools were used to appraise the quality of included studies. Data extraction was guided by the Interprofessional Shared Decision Making (IP-SDM) model. We conducted a narrative synthesis using thematic analysis. PROSPERO registration number CRD42019131497. Forty-five studies were included (20 qualitative, 15 quantitative and 10 case studies), comprising data from 17 countries and 6020 patients, family caregivers and practitioners. The studies covered a range of decisions from managing oral feeding to the use of tube feeding. We found that decisions about nutrition and hydration for people living with dementia were generally too complex to be mapped onto the precise linear steps of the existing decision-making model. Decision-making processes around feeding for people living with dementia were largely influenced by medical evidence, personal values, cultures and organizational routine. Although the process involved multiple people, family caregivers and non-physician practitioners were often excluded in making a final decision. Upon disagreement, nutrition interventions were sometimes delivered with conflicting feelings concealed by family caregivers or practitioners. Most conflicts and negative feelings were resolved by good relationship, honest communication, multidisciplinary team meetings and renegotiation. The decision-making process regarding nutrition and hydration for people living with dementia does not follow a linear process. It needs an informed, value-sensitive, and collaborative process. However, it often characterized by unclear procedures and with a lack of support. Decisional support is needed and should be approached in a shared and stepwise manner.

MeSH Terms

-

Keywords

Aging; Alzheimer’s disease; Decision making; Dehydration; Dementia; Feeding methods; Nutrition; Systematic review

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience.

Abstract

The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article.

MeSH Terms

-

Keywords

adaptive immunity; aging; innate immunity; longevity; resilience

The Human Epidermal Basement Membrane: A Shaped and Cell Instructive Platform That Aging Slowly Alters.

Abstract

One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the dermal-epidermal junction-a complex network of extracellular matrix macromolecules that connect the outer epidermal layer to the underlying dermis. This junction provides both a structural support to keratinocytes and a specific niche that mediates signals influencing their behavior. It displays a distinctive microarchitecture characterized by an undulating pattern, strengthening dermal-epidermal connectivity and crosstalk. The optimal stiffness arising from the overall molecular organization, together with characteristic anchoring complexes, keeps the dermis and epidermis layers extremely well connected and capable of proper epidermal renewal and regeneration. Due to intrinsic and extrinsic factors, a large number of structural and biological changes accompany skin aging. These changes progressively weaken the dermal-epidermal junction substructure and affect its functions, contributing to the gradual decline in overall skin physiology. Most changes involve reduced turnover or altered enzymatic or non-enzymatic post-translational modifications, compromising the mechanical properties of matrix components and cells. This review combines recent and older data on organization of the dermal-epidermal junction, its mechanical properties and role in mechanotransduction, its involvement in regeneration, and its fate during the aging process.

MeSH Terms

-

Keywords

aging; basement membrane; dermal papilla; dermal-epidermal junction; epidermal rete-ridge; extracellular matrix; mechanical properties; skin

Cellular and molecular features of senescence in acute lung injury.

Abstract

A wide range of insults can trigger acute injury in the lungs, which eventually may lead to respiratory failure and death of patients. Current treatment relies mainly on supportive measures and mechanical ventilation. Even so, survivors frequently develop important sequels that compromise quality of life. In the search for new approaches to prevent and treat acute lung injury, many investigations have focused on molecular and cellular pathways which could exert a pathogenic role in this disease. Herein, we review recent findings in the literature suggesting that cellular senescence could be involved in lung injury and discuss the potential use of senotherapies to prevent disease progression.

MeSH Terms

-

Keywords

Acute lung injury; Acute respiratory distress syndrome; Senescence

Dilated cardiomyopathy impairs mitochondrial biogenesis and promotes inflammation in an age- and sex-dependent manner.

Abstract

Dilated cardiomyopathy (DCM) belongs to the myocardial diseases associated with a severe impairment of cardiac function, but the question of how sex and age affect this pathology has not been fully explored. Impaired energy homeostasis, mitochondrial dysfunction, and systemic inflammation are well-described phenomena associated with aging. In this study, we investigated if DCM affects these phenomena in a sex- and age-related manner. We analyzed the expression of mitochondrial and antioxidant proteins and the inflammatory state in DCM heart tissue from younger and older women and men. A significant downregulation of Sirt1 expression was detected in older DCM patients. Sex-related differences were observed in the phosphorylation of AMPK that only appeared in older males with DCM, possibly due to an alternative Sirt1 regulation mechanism. Furthermore, reduced expression of several mitochondrial proteins (TOM40, TIM23, Sirt3, and SOD2) and genes ([i]cox1[/i], [i]nd4[/i]) was only detected in old DCM patients, suggesting that age has a greater effect than DCM on these alterations. Finally, an increased expression of inflammatory markers in older, failing hearts, with a stronger pro-inflammatory response in men, was observed. Together, these findings indicate that age- and sex-related increased inflammation and disturbance of mitochondrial homeostasis occurs in male individuals with DCM.

MeSH Terms

-

Keywords

aging; dilated cardiomyopathy; inflammation; mitochondrial proteins; sex differences

Bioinformatics analysis of autophagy-lysosomal degradation in cardiac aging.

Abstract

Cardiac aging, which causes cardiac diastolic dysfunction, frequently occurs in older people. The role of autophagy in cardiac aging is the subject of intensive research. Autophagy comprises steps called the autophagosome formation and autophagosome-lysosome fusion. Caloric restriction (CR) is the gold standard used to induce autophagosome formation, and autophagosome-lysosome fusion is reduced by aging. However, few studies are available that survey and compare signaling during CR (autophagosome formation induced status) and old (potentially autophagosome-lysosome fusion-reduced status). Here we aimed to identify the rate-limiting step of autophagic disorders during cardiac aging. We employed bioinformatics to analyze publicly available DNA microarray datasets. The first dataset compared the hearts of young and old C57BL6 mice (OLD). The second dataset compared the hearts of young C57BL6 mice fed a normal diet with those of young C57BL6 mice subjected to CR. We analyzed OLD-upregulated genes that were significantly associated with the Gene Ontogeny term "Autophagy," indicating that autophagic genes were upregulated in OLD mice. The autophagy-related gene Atg5 and Atg5-related genes were upregulated in OLD and CR mice. The identified hub and bottleneck genes are autophagic autophagosome formation suppressors such as Sirt2, Ilk and Islr, as well as the autophagosome-lysosome fusion inducer Snapin. Autophagosome formation genes were upregulated in aging mice subjected to CR, indicating that an upregulated autophagosome formation is not a change specific to cardiac aging. However, autophagosome-lysosome fusion genes, particularly the lysosome transportation-related gene Snapin, were downregulated in aging, indicating that autophagosome-lysosome fusion may cause autophagic disorders in cardiac aging. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.

MeSH Terms

-

Keywords

aging; autophagy; cardiology; computational biologyly; sosomes

Bridging the gap between serum biomarkers and biomechanical tests in musculoskeletal ageing.

Abstract

Musculoskeletal ageing is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Preclinical and clinical data strongly support the muscle-bone cross-talk showing the presence of many tissue-specific factors released by the muscle that modulate bone, such as insulin-like growth factor-1 (IGF- 1), IL-6, IL-15, myostatin and irisin. Bone and muscle tissues were increasingly recognized as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. It is then plausible that laboratory parameters could be involved in sarcopenia and osteoporosis diagnosis and treatment monitoring. This narrative review raises the possibility of whether this poor correlation between different muscle/lean mass assessment methods and muscle function tests could suggest that each parameter evaluates different aspects of "muscle status" or "muscle quality". If this is true, no one test can be used to assess muscle status but rather a battery of tests is necessary for a comprehensive assessment. More research is required to provide information for researchers to optimally design studies by using the muscle assessment method that is best associated with selected specific outcomes.

MeSH Terms

-

Keywords

aging; biomarker; frailty; gait; osteoporosis; sarcopenia; serum

Postural Control While Walking Interferes With Spatial Learning in Older Adults Navigating in a Real Environment.

Abstract

Cognitive demands for postural control increase with aging and cognitive-motor interference (CMI) exists for a number of walking situations, especially with visuo-spatial cognitive tasks. Such interference also influences spatial learning abilities among older adults; however, this is rarely considered in research on aging in spatial navigation. We posited that visually and physically exploring an unknown environment may be subject to CMI for older adults. We investigated potential indicators of postural control interfering with spatial learning. Given known associations between age-related alterations in gait and brain structure, we also examined potential neuroanatomical correlates of this interference. Fourteen young and 14 older adults had to find an invisible goal in an unfamiliar, real, ecological environment. We measured walking speed, trajectory efficiency (direct route over taken route) and goal fixations (proportion of visual fixations toward the goal area). We calculated the change in walking speed between the first and last trials and adaptation indices for all three variables to quantify their modulation across learning trials. All participants were screened with a battery of visuo-cognitive tests. Eighteen of our participants (10 young, 8 older) also underwent a magnetic resonance imaging (MRI) examination. Older adults reduced their walking speed considerably on the first, compared to the last trial. The adaptation index of walking speed correlated positively with those of trajectory efficiency and goal fixations, indicating a reduction in resource sharing between walking and encoding the environment. The change in walking speed correlated negatively with gray matter volume in superior parietal and occipital regions and the precuneus. We interpret older adults' change in walking speed as indicative of CMI, similar to dual task costs. This is supported by the correlations between the adaptation indices and between the change in walking speed and gray matter volume in brain regions that are important for navigation, given that they are involved in visual attention, sensory integration and encoding of space. These findings under ecological conditions in a natural spatial learning task question what constitutes dual tasking in older adults and they can lead future research to reconsider the actual cognitive burden of postural control in aging navigation research.

MeSH Terms

-

Keywords

aging; brain atrophy; cognitive-motor interference; navigation; parietal cortex; postural control; spatial learning; walking speed

Weather Woes? Exploring Potential Links between Precipitation and Age-Related Cognitive Decline.

Abstract

Rain, snow, or ice may discourage older adults from leaving their homes with potential consequences for social isolation, decreased physical activity, and cognitive decline. This study is the first to examine potential links between annual precipitation exposure and cognitive function in a large population-based cohort of older Americans. We examined the association between precipitation (percent of days with snow or rain in the past year) and cognitive function in 25,320 individuals aged 45+ from the Reasons for Geographic and Racial Differences in Stroke Study. Linear mixed models assessed the relationship between precipitation and cognitive function, as well as rates of change in cognitive function with age. We found a non-linear relationship between precipitation and cognitive function. Compared to those exposed to infrequent precipitation (less than 20% of days with rain/snow in the past year), cognitive function was higher among older adults experiencing moderately frequent precipitation (20-40% of annual days with precipitation). However, beyond more than about 45% of days with precipitation in the past year, there was a negative association between precipitation and cognitive function, with faster rates of cognitive decline with age. These exploratory findings motivate further research to better understand the complex role of precipitation for late-life cognitive function.

MeSH Terms

-

Keywords

aging; climate; cognitive function; environment; longitudinal

Review of How Genetic Research on Segmental Progeroid Syndromes Has Documented Genomic Instability as a Hallmark of Aging But Let Us Now Pursue Antigeroid Syndromes!

Abstract

The purpose of this early contribution to the new Fellows Forum of this pioneering journal for what is now called Geroscience is to provide an example of how the author's interest in using the emerging tools of human genetics has led to strong support for one of the hallmarks of aging-Genomic Instability. We shall also briefly review our emerging interests in the genetic analysis of what we have called Antigeroid Syndromes. While there has been significant progress in that direction via genetic studies of centenarians, the search for genetic pathways that make individuals unusually resistant or resilient to the ravages of specific geriatric disorders has been comparatively neglected. We refer to these disorders as Unimodal Antigeroid Syndromes. It is our hope that our young colleagues will consider research efforts in that direction.

MeSH Terms

-

Keywords

Human aging; Human genetics; Longevity; Progeroid syndromes

Medical Cannabis Use: Exploring the Perceptions and Experiences of Older Adults with Chronic Conditions.

Abstract

Although the rate of cannabis use by older adults is increasing more quickly than all other age groups, little is known about the reasons older adults use cannabis and the outcomes they experience. With this research, we investigated older adults' perceptions and experiences of medical cannabis use to treat and/or manage chronic conditions, specifically as a substitute for prescription drugs.  : Researchers relied on qualitative inquiry in the form of semi-structured, one-on-one interviewing to investigate the phenomenon of medical cannabis use for the management of chronic conditions.  : Our findings suggest that older adults are open to medical cannabis as an alternative to pharmaceutical drugs, hopeful with regard to the management of symptoms and pain, and aware of and astute at managing issues related to stigma both from their physicians and family and friends. Furthermore, older adults describe the frustrations with education, awareness, and lack of support with dosing.  : Participations found medical cannabis use to be beneficial in managing chronic conditions and alleviating symptoms such as chronic pain. Findings are presented as an interpretation of the participants' perceptions of their medical cannabis use. Implications for putting medical cannabis use into everyday practice as well as policy implications are considered.  : This information will help clinicians better support older adults desiring to use medical cannabis. This research will help clinicians learn more about factors impacting medical cannabis use, and the types of information and assistance that may aid older adults in their health and well-being with the use of medical cannabis to treat chronic conditions.

MeSH Terms

-

Keywords

Aging; health; medical cannabis; qualitative methods

Vestibular function modulates the impact of nGVS on postural control in older adults.

Abstract

Previous studies have reported an important relationship between increasing age, vestibular impairment and increased risk of falls. Recently, noisy galvanic vestibular stimulation (nGVS) has been shown to improve postural control in older adults. However, this effect of nGVS in older adults has not been examined in interaction with the integrity of the vestibular function. We aimed at determining the effect of nGVS on postural control in older adults with and without vestibular impairment and ii) at examining the sustained effect of nGVS as compared to a sham stimulation. 36 older adults were randomly assigned to the nGVS group [n=24] or the sham group [n=12]. In the nGVS group, 12 participants had normal vestibular function and 12 had vestibular impairment. Static postural control was assessed prior to stimulation, during stimulation and immediately following 30 minutes of nGVS. Results showed that nGVS induced a significant improvement in sway velocity (p<0.001) and path length (p<0.001) compared to sham stimulation. In the nGVS group, participants with vestibular impairment showed a significant decrease of sway velocity (p<0.05) and path length (p<0.05) as compared to those with normal vestibular function. Improvements in sway velocity (p<0.001) and path length (p<0.001) induced by nGVS were sustained immediately following stimulation. These findings suggest that nGVS improves postural control in older adults, and that the effect of nGVS varies depending on the integrity of the vestibular function. Results also show that nGVS effect on postural control, compared to a sham stimulation, can be sustained after the end of stimulation.

MeSH Terms

-

Keywords

Aging; Noisy galvanic vestibular stimulation; Postural control; Vestibular function; Vestibular system

Genetic Factors of Alzheimer's Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study.

Abstract

Fluid intelligence (FI) involves abstract problem-solving without prior knowledge. Greater age-related FI decline increases Alzheimer's disease (AD) risk, and recent studies suggest that certain dietary regimens may influence rates of decline. However, it is uncertain how long-term food consumption affects FI among adults with or without familial history of AD (FH) or APOE4 (ɛ4). Observe how the total diet is associated with long-term cognition among mid- to late-life populations at-risk and not-at-risk for AD. Among 1,787 mid-to-late-aged adult UK Biobank participants, 10-year FI trajectories were modeled and regressed onto the total diet based on self-reported intake of 49 whole foods from a Food Frequency Questionnaire (FFQ). Daily cheese intake strongly predicted better FIT scores over time (FH-: β= 0.207, p < 0.001; ɛ4-: β= 0.073, p = 0.008; ɛ4+: β= 0.162, p = 0.001). Alcohol of any type daily also appeared beneficial (ɛ4+: β= 0.101, p = 0.022) and red wine was sometimes additionally protective (FH+: β= 0.100, p = 0.014; ɛ4-: β= 0.59, p = 0.039). Consuming lamb weekly was associated with improved outcomes (FH-: β= 0.066, p = 0.008; ɛ4+: β= 0.097, p = 0.044). Among at risk groups, added salt correlated with decreased performance (FH+: β= -0.114, p = 0.004; ɛ4+: β= -0.121, p = 0.009). Modifying meal plans may help minimize cognitive decline. We observed that added salt may put at-risk individuals at greater risk, but did not observe similar interactions among FH- and AD- individuals. Observations further suggest in risk status-dependent manners that adding cheese and red wine to the diet daily, and lamb on a weekly basis, may also improve long-term cognitive outcomes.

MeSH Terms

-

Keywords

APOE4; Aging; Mediterranean diet; cognitive decline; functional food; lamb; nutrition policy; preventive medicine; red wine; salt

Silencing ATG6 and PI3K accelerates petal senescence and reduces flower number and shoot biomass in petunia.

Abstract

Petal senescence is a form of developmental programmed cell death (PCD) that is regulated by internal and environmental signals. Autophagy, a metabolic pathway that regulates intercellular nutrient recycling, is thought to play an important role in the regulation of petal senescence-associated PCD. To characterize the function of two central autophagy genes in petal senescence, we down-regulated Autophagy Gene 6 (PhATG6) and Phosphoinositide 3-Kinase (PhPI3K) using Virus-Induced Gene Silencing (VIGS) in Petunia × hybrida. The silencing of PhATG6 and PhPI3K accelerated petal senescence, thereby reducing flower longevity. Both PhATG6- and PhPI3K-silenced petunias had reduced flower numbers, flower biomass, and vegetative shoot biomass. These phenotypes were intensified when plants were grown under low nutrient conditions. Additionally, two important regulators of senescence, an ethylene biosynthesis gene (PhACS) and a type I metacaspase gene (PhMC1), were suppressed in senescing petals of PhATG6- and PhPI3K-silenced plants. In conclusion, our study identified PhATG6 and PhPI3K as negative regulators of flower senescence and demonstrated the influence of nutrient limitation on the function of autophagy during petal senescence. Our study also found that autophagy genes potentially influence the transcriptional regulation of metacaspases and ethylene biosynthetic genes during petal senescence. The results of this project will be fundamental for future studies of petal senescence and will provide genetic information for future crop improvement.

MeSH Terms

-

Keywords

Autophagy; Ethylene; Longevity; Metacaspase; Programmed cell death; VIGS

Higher relative effort of the knee relates to faster adaptation in older adults at risk for mobility disability.

Abstract

Gait adaptation is crucial for adults at risk for mobility disability, and executive function and physical function may be important for adaptation performance. Gait adaptation can be measured using a treadmill with two belts, known as a split-belt treadmill. Increasing evidence supports that gait adaptability, executive function, and physical function are interrelated in older adults. The purpose of this study was to determine if: a) executive function and measures of relative effort of the ankle and knee relate to split-belt treadmill adaptation; b) older adults classified as fast adapters display differences in relative effort, executive function, and propulsive impulse (push-off) compared to slow adapters; and c) spatial and temporal control differ between individuals with faster rate of adaptation compared to those with slower rates of adaptation. Greater effort of the knee on the slow belt was related to faster early adaptation (r = 0.650, p = 0.005) indicating its importance for adapting quickly to the perturbation. We did not observe a relationship between cognitive tests and adaptation performance. We did not detect any statistical differences in cognitive tests performance, push-off, spatial or temporal control between fast adapters compared to slow adapters. Our results suggest that in older adults at risk for mobility disability, higher effort at the knee is important for early split-belt adaptation.

MeSH Terms

-

Keywords

Adaptation; Aging; Cognition; Relative effort; Split-belt; Walking

The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing.

Abstract

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), [i]Faecalibacterium prausnitzii[/i] and [i]Roseburia inulinivorans[/i], and of [i]Alistipes shahii[/i]. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.

MeSH Terms

-

Keywords

frailty; geriatrics; gut microbiota; gut–muscle axis; physical function

The Gut Microbiome, Aging, and Longevity: A Systematic Review.

Abstract

Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but [i]Akkermansia[/i] was most consistently reported to be relatively more abundant with aging, whereas [i]Faecalibacterium[/i], [i]Bacteroidaceae[/i], and [i]Lachnospiraceae[/i] were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes.

MeSH Terms

-

Keywords

centenarians; cognition; functional potential; healthy aging; immunosenescence; inflammation; metabolites; microbes

Protective effects of saponins from Panax japonicus on neurons of the colon myenteric plexus in aging rats through reduction of α-synuclein through endoplasmic reticulum stress.

Abstract

The enteric nervous system degenerates gradually with age, and α-synuclein (α-syn) is a suitable marker of enteric nervous system degeneration, which is intimately related with endoplasmic reticulum stress and unfolded protein response (UPR ). Saponins from Panax japonicus (SPJ) have obvious protective effects on neurons in several degenerative disease models. Here, the study was designed to investigate whether SPJ could reverse the neuron degeneration through regulating the UPR in the colon myenteric plexus of aging rats. Aging rats had been treated with SPJ for 6 months since they were aged 18 months. Then, the colon samples were collected and neuron morphology in the myenteric plexus was observed. Immunohistochemistry staining was used to detect the expressions of NeuN, α-syn, GRP78 and three different UPR branches. Double immunofluorescence was used to determine the co-localization of α-syn and NeuN, GRP78 and NeuN. Neurons degenerated in the colon myenteric plexus of aging rats, but co-localization of α-syn and NeuN increased. In addition, both the expressions of GRP78 and three UPR branch signaling pathway proteins decreased in the colon myenteric plexus of aging rats. Treatment of SPJ almost alleviated the above effects in aging rats, except for ATF6. SPJ could reverse the neuron loss caused by accumulation of α-syn in the myenteric plexus of colon in aging rats, which is potentially associated with increased GRP78 and most URP changes. Geriatr Gerontol Int 2020; ••: ••-••.

MeSH Terms

-

Keywords

aging; myenteric plexus; saponins from Panax japonicus; unfolded protein response of endoplasmic reticulum; α-synuclein

Iron Status is Associated with Mood, Cognition, and Functional Ability in Older Adults: A Cross-Sectional Study.

Abstract

Several conditions are risk factors for iron deficiency (ID), some of which are highly prevalent in older individuals. Despite the amount of evidence pointing for a role of ID in cognition, mood and physical functional ability, the research addressing these associations in older individuals is still scarce. In the present study, 162 older community-dwelling individuals (29.53% classified as ID) were enrolled in a cross-sectional analysis and characterized regarding cognition, mood, functional ability, general nutritional intake and iron status. Assessment of iron status was performed using several blood biomarkers. Storage and erythropoiesis dimensions were positively associated with memory, along with an interaction (moderator effect) between iron storage and nutritional status. A more depressed mood was negatively associated with (iron) transport, transport saturation and erythropoiesis dimensions, and functional tiredness was positively associated with the erythropoiesis dimension. These observations indicate that lower iron status is associated with depressive mood, functional tiredness and poorer memory ability, with the latter moderated by nutritional status. These findings suggest that using iron as a continuous variable may be useful in finding associations with iron homeostasis, eventually missed when iron levels are considered within the usual classification groups.

MeSH Terms

-

Keywords

aging; cognition; iron deficiency; mood; physical functional ability

U-Shaped Association between Dietary Acid Load and Risk of Osteoporotic Fractures in 2 Populations at High Cardiovascular Risk.

Abstract

Bone contributes to maintaining the acid-base balance as a buffering system for blood pH. Diet composition also affects acid-base balance. Several studies have linked an imbalance in the acid-base system to changes in the density and structure of bone mass, although some prospective studies and meta-analyses suggest that acid load has no deleterious effect on bone. The aim of this study was to examine the associations between potential renal acid load (PRAL) and net endogenous acid production (NEAP) and the risk of osteoporotic fractures and bone mineral density (BMD) in 2 middle-aged and elderly Mediterranean populations. We conducted a longitudinal analysis including 870 participants from the PREvención con DIeta MEDiterranea (PREDIMED) Study and a cross-sectional analysis including 1134 participants from the PREDIMED-Plus study. Participants were adults, aged 55-80 y, either at high cardiovascular risk (PREDIMED) or overweight/obese with metabolic syndrome (PREDIMED-Plus), as defined by the International Diabetes Federation, the American Heart Association, and the National Heart Association. PRAL and NEAP were calculated from validated food-frequency questionnaires. BMD was measured using DXA scans. Fracture information was obtained from medical records. The association between mean PRAL and NEAP and fracture risk was assessed using multivariable-adjusted Cox models. BMD differences between tertiles of baseline PRAL and NEAP were evaluated by means of ANCOVA. A total 114 new fracture events were documented in the PREDIMED study after a mean of 5.2 y of intervention and 8.9 y of total follow-up. Participants in the first and third PRAL and NEAP tertiles had a higher risk of osteoporotic fracture compared with the second tertile, showing a characteristically U-shaped association [HR (95% CI): 1.73 (1.03, 2.91) in tertile 1 and 1.91 (1.14, 3.19) in tertile 3 for PRAL, and 1.83 (1.08, 3.09) in tertile 1 and 1.87 (1.10, 3.17) in tertile 3 for NEAP]. Compared with the participants in tertile 1, the participants in the top PRAL and NEAP tertiles had lower BMD [PRAL: mean total femur BMD: 1.029 ± 0.007 and 1.007 ± 0.007 g/cm2; P = 0.006 (tertiles 1 and 3); NEAP: mean total femur BMD: 1.032 ± 0.007 and 1.009 ± 0.007 g/cm2; P = 0.017 (tertiles 1 and 3)]. The results of our study suggest that both high and low dietary acid are associated with a higher risk of osteoporotic fractures, although only high dietary acid was found to have a negative relation to BMD in senior adults with existing chronic health conditions. This trial was registered at http://www.isrctn.com/ as ISRCTN3573963 (PREDIMED) and ISRCTN89898870 (PREDIMED-Plus).

MeSH Terms

-

Keywords

aging; bone; bone mineral density; dietary potential acid load; fracture

Exploration on the effect of predeposit autotransfusion on bone marrow hematopoiesis after femoral shaft fracture.

Abstract

By observing the changes in the number and activity of CD34+ cells in bone marrow after predeposit autotransfusion (PAT) to patients with femoral shaft fracture (FSF), to evaluate the effects of PAT on hematopoietic function and hematopoietic stem cells in bone marrow. Selected FSF patients were randomly divided into 2 groups: the control group (patients did not receive blood transfusion after surgery) and PAT group (patients received PAT after surgery). The content of RBC and Plt in blood samples were counted by blood routine. The cell cycle and proportion of CD34+ myelinated cells in blood samples was analyzed by flow cytometry. The telomere DNA length of hematopoietic stem cells (HSCs) in the control groups and PAT group at postoperation 24 was analyzed by southern blot. The content of RBC and Plt in postoperation 6h and 24h in the control group was evidently higher compared to that in PAT group, while Hb content in control group was significantly lower compared to that in PAT group. The proportion of CD34+ myelinated cells in post-transfusion 6h and postoperation 24h in PAT group was evidently higher compared to that in the control group. In PAT group, S phase at postoperation 24h was significantly larger compared to that at post-transfusion 6h. The telomere DNA length of HSCs in PAT group was longer than that in the control group. PAT can increase the number of HSC, while does not cause the abnormal aging of HSCs. PAT is suitable for postoperative blood transfusion of patients with FSF.

MeSH Terms

-

Keywords

Aging; CD34+ myelinated cells; Fracture; HSCs; PAT

Extracellular vesicles as potential tools for regenerative therapy.

Abstract

Small extracellular vesicles released by fibroblasts from young human donors diminish lipid peroxidation in senescent cells and in different old mice organs due to their enrichment in Glutathione-S-transferase Mu lipid antioxidant activity.

MeSH Terms

-

Keywords

Small extracellular vesicles; aging; glutathione-S-transferase M; lipid peroxidation; senescence

Sarcopenia: Molecular Pathways and Potential Targets for Intervention.

Abstract

Aging is associated with sarcopenia. The loss of strength results in decreased muscle mass and motor function. This process accelerates the progressive muscle deterioration observed in older adults, favoring the presence of debilitating pathologies. In addition, sarcopenia leads to a decrease in quality of life, significantly affecting self-sufficiency. Altogether, these results in an increase in economic resources from the National Health Systems devoted to mitigating this problem in the elderly, particularly in developed countries. Different etiological determinants are involved in the progression of the disease, including: neurological factors, endocrine alterations, as well as nutritional and lifestyle changes related to the adoption of more sedentary habits. Molecular and cellular mechanisms have not been clearly characterized, resulting in the absence of an effective treatment for sarcopenia. Nevertheless, physical activity seems to be the sole strategy to delay sarcopenia and its symptoms. The present review intends to bring together the data explaining how physical activity modulates at a molecular and cellular level all factors that predispose or favor the progression of this deteriorating pathology.

MeSH Terms

-

Keywords

aging; inflammation; oxidative stress; physical activity; sarcopenia; satellite cells

Periodic training of creeping solids.

Abstract

We consider disordered solids in which the microscopic elements can deform plastically in response to stresses on them. We show that by driving the system periodically, this plasticity can be exploited to train in desired elastic properties, both in the global moduli and in local "allosteric" interactions. Periodic driving can couple an applied "source" strain to a "target" strain over a path in the energy landscape. This coupling allows control of the system's response, even at large strains well into the nonlinear regime, where it can be difficult to achieve control simply by design.

MeSH Terms

-

Keywords

Poisson’s ratio; aging; allostery; plasticity

Family matters in unraveling human longevity.

Abstract

---

MeSH Terms

-

Keywords

aging; familial longevity; family; genes; longevity; social

Preparedness and response activities of the US Department of Veterans Affairs (VA) home-based primary care program around the fall 2017 hurricane season.

Abstract

Large-scale natural disasters disproportionally affect both the medically complex and the older old, groups that are responsible for most medical surge after a disaster. To understand how to ameliorate this surge, we examined the activities of the nine US Department of Veterans Affairs (VA) Home Based Primary Care (HBPC) programs impacted during the 2017 Fall Hurricane Season. Convergent mixed methods design, incorporating independently conducted qualitative and quantitative analyses. Phase One: 34 clinical staff were interviewed from the nine VA HBPC programs impacted by Hurricanes Harvey, Irma, and Maria to examine the experiences of their HBPC programs in response to the Hurricanes. Phase Two: Secondary quantitative data analysis used the VA's Corporate Data Warehouse (CDW) to examine the electronic health records of patients for these same nine sites. The emergency management activities of the HBPC programs emerged as two distinct phases: preparedness, and response and recovery. The early implementation of preparedness procedures, and coordinated post-Hurricane patient tracking, limited disruption in care and prevented significant hospitalizations among this population. Individuals aged 75 or older, who often present with multiple comorbidities and decreased functional status, typically prefer to age in their homes. Additionally, as in-home medical equipment evolves, more medically vulnerable individuals are able to receive care at home. HBPC programs, and similar programs under Medicare, connect the homebound, medically complex, older old to the greater healthcare community. Engaging with these programs both pre- and post-disasters is central to bolstering community resilience for these at-risk populations.

MeSH Terms

-

Keywords

Aging in place; Emergency preparedness; Home health agencies; Long-term care

Decreased testosterone secretion index and free testosterone level with multiple symptoms for late-onset hypogonadism identification: a nationwide multicenter study with 5980 aging males in China.

Abstract

Late-onset hypogonadism (LOH) is a syndrome in middle-aged and elderly men caused by age-related testosterone deficiency. Age-related change of total testosterone (TT) of Asian males is different from Caucasian population, suggesting difference for LOH identification in Asians. A nationwide cross-sectional study involving six centers in China was conducted. Totally 6296 men aged 40-79 were recruited. After exclusions 5980 men were left for analyses. The serum TT level, was neither decreased with aging nor correlated with most hypogonadal symptoms. Instead, ten hypogonadal symptoms were found to be significantly correlated with free testosterone and testosterone secretion index, thus were chosen to form a concise scale. Further analysis identified a level of free testosterone <210 pmol/L, testosterone secretion index <1.8, and the concise scale score ≧17 could be diagnosed as having significantly aggravated LOH. This study developed an evidence-based criteria for LOH identification in Chinese population and may be adopted in other Asians. It includes the impaired testosterone secretion ability and deficiency of bioavailable testosterone, which should be the main cause in LOH pathogenesis despite normal TT levels, as well as correlated multiple hypogonadal symptoms. Our results may guide the LOH treatment to increase testicular function of testosterone secretion and bioavailable testosterone.

MeSH Terms

-

Keywords

aging; aging male; late-onset hypogonadism; testosterone; testosterone secretion index

Polarization-resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy.

Abstract

Our previous study on rat skin showed that cumulative oxidative pressure induces profound structural and ultrastructural alterations in both rat skin epidermis and dermis during aging. Here, we aimed to investigate the biophotonic properties of collagen as a main dermal component in the function of chronological aging. We used second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) on 5 μm thick skin paraffin sections from 15-day-, 1-month- and 21-month-old rats, respectively, to analyze collagen alterations, in comparison to conventional light and electron microscopy methods. Obtained results show that polarization-resolved SHG (PSHG) images can detect collagen fiber alterations in line with chronological aging and that this method is consistent with light and electron microscopy. Moreover, the β coefficient calculated from PSHG images points out that delicate alterations lead to a more ordered structure of collagen molecules due to oxidative damage. The results of this study also open the possibility of successfully applying this fast and label-free method to previously fixed samples.

MeSH Terms

-

Keywords

chronological aging; collagen; electron microscopy; light microscopy; polarization-resolved SHG imaging; second-harmonic generation microscopy; two-photon excited fluorescence microscopy

Rest-Activity Rhythms and White Matter Microstructure Across the Lifespan.

Abstract

The purpose of this study was to examine how rest-activity (RA) rhythm stability may be associated with white matter microstructure across the lifespan in healthy adults free of significant cardiovascular risk. We analyzed multi-shell diffusion tensor images from 103 healthy young and older adults using tract-based spatial statistics (TBSS) to examine relationships between white matter microstructure and RA rhythm stability. RA measures were computed using both cosinor and non-parametric methods derived from seven days of actigraphy data. Fractional anisotropy (FA) and mean diffusivity (MD) were examined in this analysis. Because prior studies have suggested that the corpus callosum (CC) is sensitive to sleep physiology and RA rhythms, we also conducted a focused region of interest analysis on the CC. Greater rest-activity rhythm stability was associated with greater FA across both young and older adults, primarily in the corpus callosum and anterior corona radiata. This effect was not moderated by age group. While RA measures were associated with sleep metrics, RA rhythm measures uniquely accounted for the variance in white matter integrity. This study strengthens existing evidence for a relationship between brain white matter structure and RA rhythm stability in the absence of health risk factors. While there are differences in RA stability between age groups, the relationship with brain white matter was present across both young and older adults. RA rhythms may be a useful biomarker of brain health across both periods of adult development.

MeSH Terms

-

Keywords

actigraphy; aging; circadian rhythms; neuroimaging; sleep and the brain

A cell non-autonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.

Abstract

Caloric restriction (CR) improves healthspan and lifespan of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging associated diseases. In budding yeast, [i]Saccharomyces cerevisiae[/i], CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological lifespan (CLS). We found that conditioned media collected from stationary phase CR cultures extended CLS when supplemented into non-restricted (NR) cultures, suggesting a potential cell non-autonomous mechanism of CR-induced lifespan regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in lifespan regulation.

MeSH Terms

-

Keywords

Saccharomyces cerevisiae; aging; amino acid; caloric restriction; cell non-autonomous; chronological lifespan; one-carbon metabolism; serine

Frequent co-reactivation of Epstein-Barr virus in patients with cytomegalovirus viremia under immunosuppressive therapy and/or chemotherapy.

Abstract

Co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) occurs in iatrogenically immunosuppressed patients, but the clinical relevance of this is unknown. We aimed to determine the frequency of EBV reactivation in patients with CMV viremia and to explore its clinical significance. Serum or plasma CMV and EBV DNA was detected by quantitative real-time PCR in 82 patients who received immunosuppressive therapy and/or chemotherapy and underwent CMV antigenemia tests. CMV DNA was positive in 55 patients, with EBV reactivation being found in 29 of these (52.7%). EBV co-reactivation was significantly associated with aging (>64 years vs. ≤64 years, odds ratio 4.07, 95% confidence interval 1.06-15.6). When older patients were divided into two groups according to age, EBV co-reactivation occurred more frequently in early-old patients (aged 65-74 years) than in late-old patients (aged ≥75 years) (100.0% vs. 53.3%, respectively). Steroid pulse treatment was administered significantly more often in the early-old group than in those aged ≤64 years and ≥75 years (72.7% vs 27.6% vs 14.3%, respectively). Co-reactivation of EBV in patients with CMV viremia highlighted early-old patients and may reflect treatment intensity as well as immunosenescence.

MeSH Terms

-

Keywords

Cytomegalovirus; Epstein–Barr virus; chemotherapy; co-reactivation; immunosenescence; immunosuppression; older patients

Cellular metabolism and IL-6 concentrations during stimulated inflammation in small and large dog breeds' primary fibroblasts cells, as they age.

Abstract

The immune system undergoes marked changes during aging characterized by a state of chronic, low-grade inflammation, so called inflammaging. Domestic dogs are the most morphological and physiological diverse group of mammals, with the widest range in body masses for a single species. Additionally, smaller dogs tend to live significantly longer than larger dogs across all breeds. Body mass is intricately linked to mass-specific metabolism and aging rates, thus, dogs are exemplary for studies in inflammaging. Dermal fibroblasts cells play an important role in skin inflammation, and as such, are a good cell type to determine inflammatory patterns in dogs. Here, we examine aerobic and glycolytic cellular metabolism, and IL-6 concentrations in primary fibroblast cells isolated from small and large, young and old dogs when treated with lipopolysaccharide (LPS) from [i]Escherichia coli[/i] to stimulate an inflammatory phenotype. We found no differences in cellular metabolism of any group when treated with LPS. Unlike mice and humans, there was a less drastic amplification of IL-6 concentration after LPS treatment in the geriatric population of dogs compared with puppies. We also found evidence that large breed puppies have significantly less background or control IL-6 concentrations compared with small breed puppies. This implies that the patterns of inflammaging in dogs may be distinct and different from other mammals commonly studied.

MeSH Terms

-

Keywords

Body mass; Inflammaging; Lifespan

A Longitudinal Epigenetic Aging and Leukocyte Analysis of Simulated Space Travel: The Mars-500 Mission.

Abstract

Astronauts undertaking long-duration space missions may be vulnerable to unique stressors that can impact human aging. Nevertheless, few studies have examined the relationship of mission duration with DNA-methylation-based biomarkers of aging in astronauts. Using data from the six participants of the Mars-500 mission, a high-fidelity 520-day ground simulation experiment, we tested relationships of mission duration with five longitudinally measured blood DNA-methylation-based metrics: DNAmGrimAge, DNAmPhenoAge, DNA-methylation-based estimator of telomere length (DNAmTL), mitotic divisions (epigenetic mitotic clock [epiTOC2]), and pace of aging (PoA). We provide evidence that, relative to baseline, mission duration was associated with significant decreases in epigenetic aging. However, only decreases in DNAmPhenoAge remained significant 7 days post-mission. We also observed significant changes in estimated proportions of plasmablasts, CD4T, CD8 naive, and natural killer (NK) cells. Only decreases in NK cells remained significant post-mission. If confirmed more broadly, these findings contribute insights to improve the understanding of the biological aging implications for individuals experiencing long-duration space travel.

MeSH Terms

-

Keywords

DNA methylation age; Mars-500; aging; astronaut; epiTOC2; leukocytes; mitotic divisions; pace of aging; stress; telomere

Association between SIRT6 Methylation and Human Longevity in a Chinese Population.

Abstract

Sirtuin 6 gene (SIRT6) is a longevity gene that is involved in a variety of metabolic pathways, but the relationship between SIRT6 methylation and longevity has not been clarified. We conducted a case-control study on 129 residents with a family history of longevity (1 of parents, themselves, or siblings aged ≥90 years) and 86 individuals without a family history of exceptional longevity to identify the association. DNA pyrosequencing was performed to analyze the methylation status of SIRT6 promoter CpG sites. qRT-PCR and ELISA were used to estimate the SIRT6 messenger RNA (mRNA) levels and protein content. Six CpG sites (P1-P6) were identified as methylation variable positions in the SIRT6 promoter region. At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (p < 0.001 and p = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of SIRT6 decreased in the control group (p < 0.0001 and p = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (rs = -0.173, p = 0.011) and P5 sites (rs = -0.207, p = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (rs = 0.136, p = 0.046) but showed no significant correlation with the methylation rate at the P2 site. The low level of SIRT6 methylation may be a potential protective factor of Chinese longevity.

MeSH Terms

-

Keywords

DNA Methylation; Longevity; Messenger RNA; SIRT6

Aging effects on fractionation and speciation of redox-sensitive metals in artificially contaminated soil.

Abstract

Artificially contaminated soil is often used in laboratory experiments as a substitute for actual field contaminated soils. In the preparation and use of laboratory contaminated soils, questions remain as to how much and how long metals remain in labile form and in their oxidation state during the contamination process. Therefore, the objectives of this study were to determine if the speciation of added contaminants can be retained in the original form and to observe the change in lability of each element with aging time. In this study, natural soil was artificially polluted with five redox-sensitive toxic elements in their oxidized or reduced forms, i.e., As(III)/As(V), Sb(III)/Sb(V), Cr(III)/Cr(VI), Mo(VI), and W(V). Metal distribution was measured in progressive chemical fractionation using sequential extraction methods in contaminated soils after 3, 100, and 300 days of aging. The results indicated that the more strongly bound fraction of metals increased by day 100; whereas the fractions were not significantly different from those in the 300-day-aged soil. Among five metals, the ratio of weakly-bound fractions remained highest in As- and lowest in Cr-contaminated soils. The W(VI)-contaminated soil showed strong sorption without changes in speciation during aging. The oxidized or reduced metal species converged to occur as a single species under given soil conditions, regardless of the initial form of metal used to spike the soil. Both As and Sb existed as their oxidized form while Cr existed as its reduced form. The results of this study may provide a useful and practical guideline for artificial soil contamination.

MeSH Terms

-

Keywords

Redox-sensitive metals; Sequential extraction; Soil aging; Speciation; X-ray absorption spectroscopy

Twelve-Week Daily Consumption of [i]ad hoc[/i] Fortified Milk with ω-3, D, and Group B Vitamins Has a Positive Impact on Inflammaging Parameters: A Randomized Cross-Over Trial.

Abstract

A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with [i]ad hoc[/i] fortified foods seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tailored fortified milk on inflammaging and different health parameters. A double-blind randomized cross-over study was performed on forty-eight volunteers aged 63-80 years. The fortified milk was enriched with ω-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA), vitamins (25-hydroxyvitamin D, E, C, B6, B9, B12), and trace elements (zinc, selenium). The two intervention periods lasted for 12 weeks, with a 16-week washout intermission. Compared to placebo, the consumption of fortified milk increased the circulating levels of different micronutrients, including vitamins and the ω-3 index of erythrocyte membranes. Conversely, it reduced the amount of arachidonic acid, homocysteine, and ω-6/ω-3 ratio. Twelve-week daily consumption of [i]ad[/i][i]hoc[/i] fortified milk has an overall positive impact on different health parameters related to inflammaging in the elderly.

MeSH Terms

-

Keywords

aging; fortified milk; homocysteine; ω-3 index; ω-6/ω-3 ratio

ACE2/ACE imbalance and impaired vasoreparative functions of stem/progenitor cells in aging.

Abstract

Aging increases risk for ischemic vascular diseases. Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) are known to stimulate vascular regeneration. Activation of either the Mas receptor (MasR) by angiotensin-(1-7) (Ang-(1-7)) or angiotensin-converting enzyme-2 (ACE2) stimulates vasoreparative functions in HSPCs. This study tested if aging is associated with decreased ACE2 expression in HSPCs and if Ang-(1-7) restores vasoreparative functions. Flow cytometric enumeration of Lin CD45 CD34 cells was carried out in peripheral blood of male or female individuals (22-83 years of age). Activity of ACE2 or the classical angiotensin-converting enzyme (ACE) was determined in lysates of HSPCs. Lin Sca-1 cKit (LSK) cells were isolated from young (3-5 months) or old (20-22 months) mice, and migration and proliferation were evaluated. Old mice were treated with Ang-(1-7), and mobilization of HSPCs was determined following ischemia induced by femoral ligation. A laser Doppler blood flow meter was used to determine blood flow. Aging was associated with decreased number (Spearman r = - 0.598, P < 0.0001, n = 56), decreased ACE2 (r = - 0.677, P < 0.0004), and increased ACE activity (r = 0.872, P < 0.0001) (n = 23) in HSPCs. Migration or proliferation of LSK cells in basal or in response to stromal-derived factor-1α in old cells is attenuated compared to young, and these dysfunctions were reversed by Ang-(1-7). Ischemia increased the number of circulating LSK cells in young mice, and blood flow to ischemic areas was recovered. These responses were impaired in old mice but were restored by treatment with Ang-(1-7). These results suggest that activation of ACE2 or MasR would be a promising approach for enhancing ischemic vascular repair in aging.

MeSH Terms

-

Keywords

ACE2; Aging; Angiotensin-(1-7); Hematopoietic stem/progenitor cells; Ischemia

Inhibition of 3-phosphoinositide-dependent protein kinase 1 (PDK1) can revert cellular senescence in human dermal fibroblasts.

Abstract

Cellular senescence is defined as a stable, persistent arrest of cell proliferation. Here, we examine whether senescent cells can lose senescence hallmarks and reenter a reversible state of cell-cycle arrest (quiescence). We constructed a molecular regulatory network of cellular senescence based on previous experimental evidence. To infer the regulatory logic of the network, we performed phosphoprotein array experiments with normal human dermal fibroblasts and used the data to optimize the regulatory relationships between molecules with an evolutionary algorithm. From ensemble analysis of network models, we identified 3-phosphoinositide-dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. We showed that inhibition of PDK1 in senescent human dermal fibroblasts eradicates senescence hallmarks and restores entry into the cell cycle by suppressing both nuclear factor κB and mTOR signaling, resulting in restored skin regeneration capacity. Our findings provide insight into a potential therapeutic strategy to treat age-related diseases associated with the accumulation of senescent cells.

MeSH Terms

-

Keywords

PDK1; cellular senescence; network modeling; skin aging; systems biology

Laminin-111 Improves the Anabolic Response to Mechanical Load in Aged Skeletal Muscle.

Abstract

Anabolic resistance to a mechanical stimulus may contribute to the loss of skeletal muscle mass observed with age. In this study, young and aged mice were injected with saline or human LM-111 (1 mg/kg). One week later, the myotendinous junction of the gastrocnemius muscle was removed via myotenectomy (MTE), thus placing a chronic mechanical stimulus on the remaining plantaris muscle for two weeks. LM-111 increased α7B integrin protein expression and clustering of the α7B integrin near DAPI + nuclei in aged muscle in response to MTE. LM-111 reduced CD11b + immune cells, enhanced repair, and improved the growth response to loading in aged plantaris muscle. These results suggest that LM-111 may represent a novel therapeutic approach to prevent and/or treat sarcopenia.

MeSH Terms

-

Keywords

aging; chronic mechanical loading; extracellular matrix; hypertrophy; integrin

Attitudes of Polish Seniors toward the Use of Public Space during the First Wave of the COVID-19 Pandemic.

Abstract

The number of seniors rises worldwide. The lockdown of public institutions caused by COVID-19 influenced the lives of many of them. In the new reality, owners and managers of public spaces need to rethink the way they provide their services, and redesign public spaces to meet the needs of senior citizens. This requires the recognition of the needs of seniors concerning the use of public spaces in the times of the COVID-19 hazard. To investigate this issue, survey studies with 1000 respondents aged 65+ were conducted. The implementation of the obtained data in the process of redesigning public spaces may facilitate the opening up after the lockdown. Taking into account the requirements of a very large group of citizens being seniors is crucial, as it was found that 55% of respondents will also be afraid to use public spaces after the COVID-19 lockdown. The selected ideas that could minimize the feeling of fear when using public spaces after the lockdown were evaluated by seniors.

MeSH Terms

-

Keywords

aging population; coronavirus; design; furniture; lockdown; public areas

Aging of Brain Related with Mitochondrial Dysfunctions.

Abstract

Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signal the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insight on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

MeSH Terms

-

Keywords

Aging; Mitochondria; Synaptic plasticity; biomarkers; membrane permeability; metabolic morbidity; neuropsychiatric symptoms

Prediction of resting energy expenditure in healthy older adults: A systematic review.

Abstract

Estimates of energy requirements, based on measured or predicted resting energy expenditure (REE), are needed to avoid undernutrition or overnutrition (and their clinical consequences) in elderly subjects. The aims of this systematic review were to evaluate the prediction accuracy of REE in healthy elderly subjects and to ascertain which equation is more reliable at group level and/or individual level. Studies assessing prediction of REE in general elderly population were systematically searched using PubMed, EMBASE, Web of Science and CINAHL until March 2020. Prediction accuracy of REE was assessed at both group (bias) and individual (precision) level for each equation. Fourteen studies met the inclusion criteria of this systematic review. Bias was reported in 8 papers and calculated in another 5 from absolute values. There was a prevalent tendency towards an overestimation of REE across the studies. The least bias was observed for the Mifflin (-0.3%) and Harris-Benedict (+2.6%) equations, with values above 5% for the FAO/WHO/UNU, Fredrix and Muller equations. Precision widely varied between studies for the same equation. The higher precision was observed using the Harris-Benedict equation (~70%), while the Henry and Mifflin equations provided estimates within 10% of measured values in 65% and 61% of elderly individuals, respectively. None of the prediction equations considered provides accurate and precise REE estimates in healthy older adults. However, the best prediction is given by the Mifflin equation at group level and by the Harris-Benedict equation at individual level. Further studies with strong quality design are needed to evaluate the variability and accuracy of REE in the elderly general population.

MeSH Terms

-

Keywords

Aging; Energy requirements; Indirect calorimetry; Resting metabolic rate

Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro.

Abstract

Proteins in the eye lens have negligible turnover and therefore progressively accumulate chemical modifications during aging. Carbonyls and oxidative stresses, which are intricately linked to one another, predominantly drive such modifications. Oxidative stress leads to the loss of glutathione (GSH) and ascorbate degradation; this in turn leads to the formation of highly reactive dicarbonyl compounds that react with proteins to form advanced glycation end products (AGEs). The formation of AGEs leads to the crosslinking and aggregation of proteins contributing to lens aging and cataract formation. To inhibit AGE formation, we developed a disulfide compound linking GSH diester and mercaptoethylguanidine, and we named it carboxitin. Bovine lens organ cultured with carboxitin showed higher levels of GSH and mercaptoethylguanidine in the lens nucleus. Carboxitin inhibited erythrulose-mediated mouse lens protein crosslinking, AGE formation and the formation of 3-deoxythreosone, a major ascorbate-derived AGE precursor in the human lens. Carboxitin inhibited the glycation-mediated increase in stiffness in organ-cultured mouse lenses measured using compressive mechanical strain. Delivery of carboxitin into the lens increases GSH levels, traps dicarbonyl compounds and inhibits AGE formation. These properties of carboxitin could be exploited to develop a therapy against the formation of AGEs and the increase in stiffness that causes presbyopia in aging lenses.

MeSH Terms

-

Keywords

Aging; Carboxitin; Glycation; Lens; Mass spectrometry; Presbyopia; Protein crosslinking

Sleep disturbances and the speed of multimorbidity development in old age: results from a longitudinal population-based study.

Abstract

Sleep disturbances are prevalent among older adults and are associated with various individual diseases. The aim of this study was to investigate whether sleep disturbances are associated with the speed of multimorbidity development among older adults. Data were gathered from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study of subjects aged 60+ (N = 3363). The study included a subsample (n = 1189) without multimorbidity at baseline (< 2 chronic diseases). Baseline sleep disturbances were derived from the Comprehensive Psychiatric Rating Scale and categorized as none, mild, and moderate-severe. The number of chronic conditions throughout the 9-year follow-up was obtained from clinical examinations. Linear mixed models were used to study the association between sleep disturbances and the speed of chronic disease accumulation, adjusting for sex, age, education, physical activity, smoking, alcohol consumption, depression, pain, and psychotropic drug use. We repeated the analyses including only cardiovascular, neuropsychiatric, or musculoskeletal diseases as the outcome. Moderate-severe sleep disturbances were associated with a higher speed of chronic disease accumulation (ß/year = 0.142, p = 0.008), regardless of potential confounders. Significant positive associations were also found between moderate-severe sleep disturbances and neuropsychiatric (ß/year = 0.041, p = 0.016) and musculoskeletal (ß/year = 0.038, p = 0.025) disease accumulation, but not with cardiovascular diseases. Results remained stable when participants with baseline dementia, cognitive impairment, or depression were excluded. The finding that sleep disturbances are associated with faster chronic disease accumulation points towards the importance of early detection and treatment of sleep disturbances as a possible strategy to reduce chronic multimorbidity among older adults.

MeSH Terms

-

Keywords

Aging; Cardiovascular; Multimorbidity; Musculoskeletal; Neuropsychiatric; Sleep disturbances

Anterolateral entorhinal cortex volume is associated with memory retention in clinically unimpaired older adults.

Abstract

The entorhinal cortex is subdivided into anterolateral entorhinal cortex (alERC) and posteromedial entorhinal cortex (pmERC) subregions, which are theorized to support distinct cognitive roles. This distinction is particularly important as the alERC is one of the earliest cortical regions affected by Alzheimer's pathology and related neurodegeneration. The relative associations of alERC/pmERC with neuropsychological test performance have not been examined. We examined how alERC/pmERC volumes differentially relate to performance on 1) the Modified Rey Auditory Learning Test (ModRey), a verbal memory test designed to assess normal/preclinical populations, 2) the Montreal Cognitive Assessment (MoCA), and 3) the National Alzheimer's Coordinating Center neuropsychological battery. We also examined whether alERC/pmERC volumes correlate with Alzheimer's disease cerebrospinal fluid (CSF) biomarkers. In 65 cognitively healthy (CDR = 0) older adults, alERC, but not pmERC, volume was associated with ModRey memory retention. Only alERC volume differentiated between participants who scored above and below the MoCA cutoff score for impairment. Evaluating the MoCA subdomains revealed that alERC was particularly associated with verbal recall. On the National Alzheimer's Coordinating Center battery, both alERC and pmERC volumes were associated with Craft story recall and Benson figure copy, but only alERC volume was associated with Craft story retention and semantic fluency. Neither alERC nor pmERC volume correlated with CSF levels of amyloid or tau, and regression analyses showed that alERC volume and CSF amyloid levels were independently associated with ModRey retention performance. Taken together, these results suggest that the alERC is important for memory performance and that alERC volume differences are related to a pattern of neuropsychological test performance (i.e., impairments in episodic memory and semantic fluency) typically seen in clinical Alzheimer's disease.

MeSH Terms

-

Keywords

Aging; Amyloid; Entorhinal cortex; Memory; Neuropsychology

Adaptive response of resistant cancer cells to chemotherapy.

Abstract

Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy.

MeSH Terms

-

Keywords

Cancer; ER stress signaling; adaptive response; autophagy; chemoresistance; chemotherapy; senescence

Transglutaminase 2 Inhibitor LDN 27219 Age-Dependently Lowers Blood Pressure and Improves Endothelium-Dependent Vasodilation in Resistance Arteries.

Abstract

Transglutaminase 2 (TG2) is an enzyme which in the open conformation exerts transamidase activity, leading to protein cross-linking and fibrosis. In the closed conformation, TG2 participates in transmembrane signaling as a G protein. The unspecific transglutaminase inhibitor cystamine causes vasorelaxation in rat resistance arteries. However, the role of TG2 conformation in vascular function is unknown. We investigated the vascular effects of selective TG2 inhibitors by myography in isolated rat mesenteric and human subcutaneous resistance arteries, patch-clamp studies on vascular smooth muscle cells, and blood pressure measurements in rats and mice. LDN 27219 promoted the closed TG2 conformation and inhibited transamidase activity in mesenteric arteries. In contrast to TG2 inhibitors promoting the open conformation (Z-DON, VA5), LDN 27219 concentration-dependently relaxed rat and resistance human arteries by a mechanism dependent on nitric oxide, large-conductance calcium-activated and voltage-gated potassium channels 7, lowering blood pressure. LDN 27219 also potentiated acetylcholine-induced relaxation by opening potassium channels in the smooth muscle; these effects were abolished by membrane-permeable TG2 inhibitors promoting the open conformation. In isolated arteries from 35- to 40-week-old rats, transamidase activity was increased, and LDN 27219 improved acetylcholine-induced relaxation more than in younger rats. Infusion of LDN 27219 decreased blood pressure more effectively in 35- to 40-week than 12- to 14-week-old anesthetized rats. In summary, pharmacological modulation of TG2 to the closed conformation age-dependently lowers blood pressure and, by opening potassium channels, potentiates endothelium-dependent vasorelaxation. Our findings suggest that promoting the closed conformation of TG2 is a potential strategy to treat age-related vascular dysfunction and lowers blood pressure.

MeSH Terms

-

Keywords

aging; blood pressure; fibrosis; nitric oxide; potassium channels

Thymus involution sets the clock of declined immunity and repair with aging.

Abstract

Aging is generally characterized as a gradual increase in tissue damage, which is associated with senescence and chronic systemic inflammation and is evident in a variety of age-related diseases. The extent to which such tissue damage is a result of a gradual decline in immune regulation, which consequently compromises the capacity of the body to repair damages, has not been fully explored. Whereas CD4 T lymphocytes play a critical role in the orchestration of immunity, thymus involution initiates gradual changes in the CD4 T-cell landscape, which may significantly compromise tissue repair. In this review, we describe the lifespan accumulation of specific dysregulated CD4 T-cell subsets and their coevolution with systemic inflammation in the process of declined immunity and tissue repair capacity with age. Then, we discuss the process of thymus involution-which appears to be most pronounced around puberty-as a possible driver of the aging T-cell landscape. Finally, we identify individualized T cell-based early diagnostic biomarkers and therapeutic strategies for age-related diseases.

MeSH Terms

-

Keywords

Aging; Chronic systemic inflammation; Dysregulated CD4 T cells; Immune-mediated repair; Thymus

A meta-analysis of heavy metal bioavailability response to biochar aging: Importance of soil and biochar properties.

Abstract

Biochar has been widely applied to remediate the heavy metal-polluted soils, whereas biochar aging can induce the changes of the biochar physic-chemical properties. Afterwards, the bioavailability of heavy metals (BHM) will vary in soils which likely increase the unstable fractions of heavy metals and the following environmental risks. To explore the biochar aging effects on the BHM changes in responses to the variation of experimental conditions and biochar properties, a meta-analysis for the literatures published before May 2020 was conducted. A sum of 257 independent observations from 22 published papers was obtained. The results from the analysis of boosted regression tree showed that the soil pH was the most important factor influencing the BHM changes in biochar amended soil, followed by soil texture, aging time and biochar pyrolysis temperature. The results of this review showed that the BHM was decreased by 16.9%, 28.7% and 6.4% in weakly acid soil (pH 6.00-6.99), coarse- and medium-textured soils, respectively, but increased by 149% and 121% in the alkaline (pH > 8.00) and fine-textured soils. The BHM declined in the soils amended with biochar pyrolyzed at relative high temperature (> 500 °C), and increased during aging in soils amended with biochar pyrolyzed at relatively low temperature (401-500 °C). In terms of diverse immobilized heavy metals, only bioavailable Zn in soil decreased after aging. However, there was no significant changes in Cd, Cu and Pb's bioavalability. Besides, the BHM was decreased by 18.6% within the short-term (less than one year) biochar aging, while showed inverse trend during the longer aging processes. Besides, the application of lignin-enriched biochar may counteract the positive effects of the biochar aging on BHM. Our works may promote the interpretation of the interference factors on the BHM changes and filled the research gaps on biochar aging process in soils.

MeSH Terms

-

Keywords

Bioavailability; Biochar aging; Heavy metal; Immobilization; Meta-analysis

Lower Cardiac Output Relates to Longitudinal Cognitive Decline in Aging Adults.

Abstract

Subclinical reductions in cardiac output correspond to lower cerebral blood flow (CBF), placing the brain at risk for functional changes. This study aims to establish the consequences of reduced cardiac output on longitudinal cognitive outcomes in aging adults. Vanderbilt Memory and Aging Project participants free of clinical dementia and heart failure ([i]n[/i] = 306, 73 ± 7, 58% male) underwent baseline echocardiography to assess cardiac output (L/min) and longitudinal neuropsychological assessment at baseline, 18 months, 3 and 5 years. Linear mixed-effects regressions related cardiac output to trajectory for each longitudinal neuropsychological outcome, adjusting for age, sex, race/ethnicity, education, body surface area, Framingham Stroke Risk Profile score, apolipoprotein E ([i]APOE[/i]) ε4 status and follow-up time. Models were repeated, testing interactions with cognitive diagnosis and [i]APOE-[/i]ε4 status. Lower baseline cardiac output related to faster declines in language (β = 0.11, [i]p[/i] = 0.01), information processing speed (β = 0.31, [i]p[/i] = 0.006), visuospatial skills (β = 0.09, [i]p[/i] = 0.03), and episodic memory (β = 0.02, [i]p[/i] = 0.001). No [i]cardiac output x cognitive diagnosis[/i] interactions were observed ([i]p[/i] > 0.26). [i]APOE[/i]-ε4 status modified the association between cardiac output and longitudinal episodic memory (β = 0.03, [i]p[/i] = 0.047) and information processing speed outcomes (β = 0.55, [i]p[/i] = 0.02) with associations stronger in [i]APOE-[/i]ε4 carriers. The present study provides evidence that even subtle reductions in cardiac output may be associated with more adverse longitudinal cognitive health, including worse language, information processing speed, visuospatial skills, and episodic memory performances. Preservation of healthy cardiac functioning is important for maintaining optimal brain aging among older adults.

MeSH Terms

-

Keywords

aging; apolipoprotein E ε4; cardiac function; cognitive decline; mild cognitive impairment

Ergothioneine Mitigates Telomere Shortening under Oxidative Stress Conditions.

Abstract

Shortened telomeres are associated with aging and age-related diseases. Oxidative stress is thought to be a major contributor to telomere shortening, and antioxidants may be able to mitigate these effects. Ergothioneine is a naturally occurring amino acid with potent antioxidant properties. In order to investigate ergothioneine's effects on telomere length, we cultured primary human fibroblasts under standard and oxidative (10 µM H O ) conditions and treated cells with 0.04, 0.1, 0.3, or 1.0 mg/ml ergothioneine for 8 weeks. Telomere length measurements were performed using high-throughput quantitative fluorescent in situ hybridization (HT Q-FISH). Treatment with ergothioneine transiently increased relative telomerase activity after 24 h ([i]p[/i] < 0.05 for all concentrations). Under oxidative conditions, ergothioneine treatment resulted in significantly longer median telomere length and 20 percentile telomere length, and significantly reduced the percentage of short telomeres (<3 kilobase pairs) for all treatment concentrations after 8 weeks. Telomere shortening rate was also reduced. Overall, ergothioneine demonstrated beneficial effects by decreasing the rate of telomere shortening and preserving telomere length under oxidative stress conditions. Our data support a potential role for ergothioneine in oxidative stress-related conditions and healthy aging.

MeSH Terms

-

Keywords

aging; antioxidants; ergothioneine; telomerase; telomeres

Discovery of 4H-chromeno[2,3-d]pyrimidin-4-one derivatives as senescence inducers and their senescence-associated antiproliferative activities on cancer cells using advanced phenotypic assay.

Abstract

Current research suggests therapy-induced senescence (TIS) of cancer cells characterized by distinct morphological and biochemical phenotypic changes represent a novel functional target that may enhance the effectiveness of cancer therapy. In order to identify novel small-molecule inducers of cellular senescence and determine the potential to be used for the treatment of melanoma, a new method of high-throughput screening (HTS) and high-contents screening (HCS) based on the detection of morphological changes was designed. This image-based and whole cell-based technology was applied to screen and select a novel class of antiproliferative agents on cancer cells, 4H-chromeno[2,3-d]pyrimidin-4-one derivatives, which induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. To evaluate structure-activity relationship (SAR) study of 4H-chromeno[2,3-d]pyrimidin-4-one scaffold starting from hit 3, a focused library containing diversely modified analogues was constructed and which led to the identification of 38, a novel compound to have remarkable anti-melanoma activity in vitro with good metabolic stability.

MeSH Terms

-

Keywords

Antiproliferative agents; High-contents screening; High-throughput screening; Melanoma; Senescence; Structure-activity relationship

Age and education as factors associated with medication literacy: a community pharmacy perspective.

Abstract

Aging implies a higher prevalence of chronic pathologies and a corresponding increase in medication. The correct adherence and use of the medication are prerequisites for reducing risks of disease progression, comorbidity, and mortality. Medication literacy (ML) is the specific ability to safely access and understand the information available concerning medication, and to act accordingly. Currently, there are few specific instruments that ascertain the extent of ML in the general population. The aim of this work was to analyse ML in a large cohort of pharmacy customers. A total of 400 community pharmacy clients were analyzed to assess the level of ML (documental and numeracy) through the validated MedLitRxSE tool. The results showed that out of a total of 400 community pharmacy clients only 136 (34%) had an adequate degree of ML, while the rest of the clients (n = 264; 66%) were adjudged not to have this ability. Statistically significant differences were found between the different age groups in terms of ML (P < 0.001; OR = 0.312; 95% CI: 0.195-0.499), the 51-65 and >65-year age groups having a lower frequency of adequate ML (23.5 and 7.1%, respectively) than the rest of the age groups. A statistically significant increase in adequate ML was observed as the academic level of the clients increased (P < 0.001; OR = 15.403; 95% CI: 8.109-29.257). Multivariate logistic regression confirmed the influence of both variables on ML. An inadequate ML level was found in community pharmacy clients over the age of 51, and also in those with primary or non-formal studies. Our data add to our knowledge about ML, and should pharmacists and other health professionals to adopt new strategies to prevent, or at least reduce, errors in taking medicines, thus avoiding the undesirable effects of any misuse.

MeSH Terms

-

Keywords

Aging; Community pharmacy; Education; Legal medicine; Patient safety

Small molecule cognitive enhancer reverses age-related memory decline in mice.

Abstract

With increased life expectancy, age-associated cognitive decline becomes a growing concern, even in the absence of recognizable neurodegenerative disease. The integrated stress response (ISR) is activated during aging and contributes to age-related brain phenotypes. We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Furthermore, ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. At the cellular level in the hippocampus, ISR inhibition (i) rescues intrinsic neuronal electrophysiological properties, (ii) restores spine density and (iii) reduces immune profiles, specifically interferon and T cell-mediated responses. Thus, pharmacological interference with the ISR emerges as a promising intervention strategy for combating age-related cognitive decline in otherwise healthy individuals.

MeSH Terms

-

Keywords

ISR; aging; immune dysfunction; memory; mouse; neuroscience

Modal lifespan and disparity at older ages by leading causes of death: a Canada-U.S. comparison.

Abstract

The U.S. elderly experience shorter lifespans and greater variability in age at death than their Canadian peers. In order to gain insight on the underlying factors responsible for the Canada-U.S. old-age mortality disparities, we propose a cause-of-death analysis. Accordingly, the objective of this paper is to compare levels and trends in cause-specific modal age at death ([i]M[/i]) and standard deviation above the mode ([i]SD[/i]([i]M[/i] +)) between Canada and the U.S. since the 1970s. We focus on six broad leading causes of death, namely cerebrovascular diseases, heart diseases, and four types of cancers. Country-specific [i]M[/i] and [i]SD[/i]([i]M[/i] +) estimates for each leading cause of death are calculated from [i]P[/i]-spline smooth age-at-death distributions obtained from detailed population and cause-specific mortality data. Our results reveal similar levels and trends in [i]M[/i] and [i]SD[/i]([i]M[/i] +) for most causes in the two countries, except for breast cancer (females) and lung cancer (males), where differences are the most noticeable. In both of these instances, modal lifespans are shorter in the U.S. than in Canada and U.S. old-age mortality inequalities are greater. These differences are explained in part by the higher stratification along socioeconomic lines in the U.S. than in Canada regarding the adoption of health risk behaviours and access to medical services.

MeSH Terms

-

Keywords

Canada; Causes of death; Lifespan inequalities; Modal age at death; Mortality at older ages; U.S.

Stimulus transformation into motor action: Dynamic graph analysis reveals a posterior-to-anterior shift in brain network communication of older subjects.

Abstract

Cognitive performance slows down with increasing age. This includes cognitive processes that are essential for the performance of a motor act, such as the slowing down in response to an external stimulus. The objective of this study was to identify aging-associated functional changes in the brain networks that are involved in the transformation of external stimuli into motor action. To investigate this topic, we employed dynamic graphs based on phase-locking of Electroencephalography signals recorded from healthy younger and older subjects while performing a simple visually-cued finger-tapping task. The network analysis yielded specific age-related network structures varying in time in the low frequencies (2-7 Hz), which are closely connected to stimulus processing, movement initiation and execution in both age groups. The networks in older subjects, however, contained several additional, particularly interhemispheric, connections and showed an overall increased coupling density. Cluster analyses revealed reduced variability of the subnetworks in older subjects, particularly during movement preparation. In younger subjects, occipital, parietal, sensorimotor and central regions were-temporally arranged in this order-heavily involved in hub nodes. Whereas in older subjects, a hub in frontal regions preceded the noticeably delayed occurrence of sensorimotor hubs, indicating different neural information processing in older subjects. All observed changes in brain network organization, which are based on neural synchronization in the low frequencies, provide a possible neural mechanism underlying previous fMRI data, which report an overactivation, especially in the prefrontal and pre-motor areas, associated with a loss of hemispheric lateralization in older subjects.

MeSH Terms

-

Keywords

hemispheric asymmetry reduction in older adults (HAROLD); information processing; low frequencies; motor execution; phase locking of EEG signals; posterior-anterior shift in aging (PASA)

The Effect of MicroRNA-Mediated Exercise on Delaying Sarcopenia in Elderly Individuals.

Abstract

Sarcopenia is often regarded as an early sign of weakness and is the core element of muscle weakness in elderly individuals. Sarcopenia is closely related to the reduction of exercise, and elderly individuals often suffer from decreased muscle mass and function due to a lack of exercise. At present, studies have confirmed that resistance and aerobic exercise are related to muscle mass, strength and fiber type and to the activation and proliferation of muscle stem cells (MuSCs). Increasing evidence shows that microRNAs (miRNAs) play an important role in exercise-related changes in the quantity, composition and function of skeletal muscle. At the cellular level, miRNAs have been shown to regulate the proliferation and differentiation of muscle cells. In addition, miRNAs are related to the composition and transformation of muscle fibers and involved in the transition of MuSCs from the resting state to the activated state. Therefore, exercise may delay sarcopenia in elderly individuals by regulating miRNAs in skeletal muscle. In future miRNA-focused treatment strategies, these studies will provide valuable information for the formulation of exercise methods and will provide useful and targeted exercise programs for elderly individuals with sarcopenia.

MeSH Terms

-

Keywords

aerobic exercise; aging; microRNAs; resistance exercise; sarcopenia

The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma.

Abstract

Late-onset asthma (LOA) is beginning to account for an increasing proportion of asthma patients, which is often underdiagnosed in the elderly. Studies on the possible relations between aging-related genes and LOA contribute to the diagnosis and treatment of LOA. Forkhead Box O3 (FOXO3) and TP53 are two classic aging-related genes. DNA methylation varies greatly with age which may play an important role in the pathogenesis of LOA. We supposed that the differentially methylated sites of FOXO3 and TP53 associated with clinical phenotypes of LOA may be useful biomarkers for the early screening of LOA. The mRNA expression and DNA methylation of FOXO3 and TP53 in peripheral blood of 43 LOA patients (15 mild LOA, 15 moderate LOA and 13 severe LOA) and 60 healthy controls (HCs) were determined. The association of methylated sites with age was assessed by Cox regression to control the potential confounders. Then, the correlation between differentially methylated sites (DMSs; p-value < 0.05) and clinical lung function in LOA patients was evaluated. Next, candidate DMSs combining with age were evaluated to predict LOA by receiver operating characteristic (ROC) analysis and principal components analysis (PCA). Finally, HDM-stressed asthma model was constructed, and DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-AZA) were used to determine the regulation of DNA methylation on the expression of FOXO3 and TP53. Compared with HCs, the mRNA expression and DNA methylation of FOXO3 and TP53 vary significantly in LOA patients. Besides, 8 DMSs from LOA patients were identified. Two of the DMSs, chr6:108882977 (FOXO3) and chr17:7591672 (TP53), were associated with the severity of LOA. The combination of the two DMSs and age could predict LOA with high accuracy (AUC values = 0.924). In HDM-stressed asthma model, DNA demethylation increased the expression of FOXO3 and P53. The mRNA expression of FOXO3 and TP53 varies significantly in peripheral blood of LOA patients, which may be due to the regulation of DNA methylation. FOXO3 and TP53 methylation is a suitable blood biomarker to predict LOA, which may be useful targets for the risk diagnosis and clinical management of LOA.

MeSH Terms

-

Keywords

Aging; DNA methylation; FOXO3; Late-onset asthma; TP53

Comparison of basal whole-body protein kinetics and muscle protein synthesis between young and older adults.

Abstract

Significant research has been dedicated to counteracting age-related muscle loss, but underlying mechanisms have not been clearly established. Previous research examining differences in basal protein kinetics between young and older individuals has been limited by a lack of evaluation of protein breakdown and net balance. The aim of this study was to more comprehensively examine differences in basal protein kinetics between younger and older males and females. Basal whole-body protein kinetics and muscle fractional synthetic rate (FSR) from 91 younger (18-38 years; 52% female) and 66 older (51-81 years; 53% female) healthy adults were determined using stable isotope tracer techniques (L-[ring- H ]phenylalanine and L-[ring- H ]tyrosine). There were no group × sex interaction effects (p > .05). Older individuals had greater whole-body protein synthesis (mean difference old-young (Δ) ± SE: 28.54 ± 8.15 mg/kg LBM/hr; p = .001) and breakdown (Δ: 15.44 ± 7.33 mg/kgLBM/hr; p = .038), but a less negative net balance (Mean ± SD: Young: -31.22 ± 7.42 mg/kg LBM/hr; Old: -18.11 ± 21.60 mg/kg LBM/hr; p < .001) compared to young individuals. Basal FSR was not significantly different between young and older (Δ: 0.007 ± 0.003%/hr; p = .052). Across the age range, females had greater whole-body protein turnover (PSΔ: 19.10 ± 7.00 mg/kgLBM/hr; PBΔ: 19.22 ± 6.31 mg/kgLBM/hr; p < .01) compared to males. Results demonstrate a difference in basal whole-body protein kinetics between young and older adults, with older adults having a higher protein turnover rate and a less negative net balance. Across the age range, females were also found to have a higher turnover rate compared to males. Differences may represent a shift in older physiology toward mechanisms that increase the efficiency of amino acid reutilization, especially in women.

MeSH Terms

-

Keywords

aging; anabolic resistance; protein metabolism; sarcopenia; stable isotopes

ASB7 Is a Novel Regulator of Cytoskeletal Organization During Oocyte Maturation.

Abstract

Ankyrin repeat and SOCS box (ASB) family members have a [i]C[/i]-terminal SOCS box and an [i]N[/i]-terminal ankyrin-related sequence of variable repeats. To date, the roles of ASB family members remain largely unknown. In the present study, by employing knockdown analysis, we investigated the effects of ASB7 on mouse oocyte meiosis. We show that specific depletion of ASB7 disrupts maturational progression and meiotic apparatus. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are frequently observed in ASB7-abated oocytes. Consistent with this observation, incidence of aneuploidy is increased in these oocytes. Meanwhile, confocal scanning reveals that loss of ASB7 impairs kinetochore-microtubule interaction and provokes the spindle assembly checkpoint during oocyte meiosis. Furthermore, we find a significant reduction of ASB7 protein in oocytes from aged mice. Importantly, increasing ASB7 expression is capable of partially rescuing the maternal age-induced meiotic defects in oocytes. Together, our data identify ASB7 as a novel player in regulating cytoskeletal organization and discover the potential effects of ASB7 on quality control of aging oocytes.

MeSH Terms

-

Keywords

ASBs; maternal aging; meiosis; oocyte; reproduction

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging.

Abstract

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic ([i]ob[/i]/[i]ob[/i]) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

MeSH Terms

-

Keywords

4-HHE (4-hydroxy hexenal); 4-HNE (4-hydroxynonenal); adipose; aging; carbonylation; epigenomics; histone

Comparison of morphometric, structural, mechanical, and physiologic characteristics of human superficial femoral and popliteal arteries.

Abstract

Peripheral arterial disease differentially affects the superficial femoral (SFA) and the popliteal (PA) arteries, but their morphometric, structural, mechanical, and physiologic differences are poorly understood. SFAs and PAs from 125 human subjects (age 13-92, average 52±17 years) were compared in terms of radii, wall thickness, and opening angles. Structure and vascular disease were quantified using histology, mechanical properties were determined with planar biaxial extension, and constitutive modeling was used to calculate the physiologic stress-stretch state, elastic energy, and the circumferential physiologic stiffness. SFAs had larger radii than PAs, and both segments widened with age. Young SFAs were 5% thicker, but in old subjects the PAs were thicker. Circumferential (SFA: 96→193°, PA: 105→139°) and longitudinal (SFA: 139→306°, PA: 133→320°) opening angles increased with age in both segments. PAs were more diseased than SFAs and had 11% thicker intima. With age, intimal thickness increased 8.5-fold, but medial thickness remained unchanged (620μm) in both arteries. SFAs had 30% more elastin than the PAs, and its density decreased ~50% with age. SFAs were more compliant than PAs circumferentially, but there was no difference longitudinally. Physiologic circumferential stress and stiffness were 21% and 11% higher in the SFA than in the PA across all ages. The stored elastic energy decreased with age (SFA: 1.4→0.4kPa, PA: 2.5→0.3kPa). While the SFA and PA demonstrate appreciable differences, most of them are due to vascular disease. When pathology is the same, so are the mechanical properties, but not the physiologic characteristics that remain distinct due to geometrical differences.

MeSH Terms

-

Keywords

Aging; Constitutive modeling; Mechanical properties; Popliteal artery; Regional differences; superficial femoral artery

Nutrient Signaling, Stress Response, and Inter-organelle Communication Are Non-canonical Determinants of Cell Fate.

Abstract

Isogenic cells manifest distinct cellular fates for a single stress; however, the nongenetic mechanisms driving such fates remain poorly understood. Here, we implement a robust multi-channel live-cell imaging approach to uncover noncanonical factors governing cell fate. We show that in response to acute glucose removal (AGR), budding yeast undergoes distinct fates, becoming either quiescent or senescent. Senescent cells fail to resume mitotic cycles following glucose replenishment but remain responsive to nutrient stimuli. Whereas quiescent cells manifest starvation-induced adaptation, senescent cells display perturbed endomembrane trafficking and defective nucleus-vacuole junction (NVJ) expansion. Surprisingly, senescence occurs even in the absence of lipid droplets. Importantly, we identify the nutrient-sensing kinase Rim15 as a key biomarker predicting cell fates before AGR stress. We propose that isogenic yeast challenged with acute nutrient shortage contains determinants influencing post-stress fate and demonstrate that specific nutrient signaling, stress response, trafficking, and inter-organelle biomarkers are early indicators for long-term fate outcomes.

MeSH Terms

-

Keywords

Bayesian analysis; LD; NVJ; cell cycle; cellular decision making; lipid droplet; nucleus-vacuole junction; quantitative imaging; quiescence; senescence; statistical evidence

Winter of our contentment: Examining risk, pleasure, and emplacement in later-life physical activity.

Abstract

In the West, many in the media and the health sector emphasize physical activity as important for the old, so that they can circumvent the impacts of aging and the associated costs. At the same time, neoliberal health discourse advises older people to avoid activities that may cause injuries, such as slips and falls, creating contradictions for older people who participate in sports on ice. In light of these mixed messages, this paper explores how older men understand their bodies through their participation in the seemingly risky sport of ice hockey. I conducted eighteen semi-structured interviews with older Canadian men who played hockey, identifying common themes related to aging, embodiment, risk and pleasure. Participants were aware that common-sense discourse produced hockey as risky for the old, but often downplayed this risk, privileging pleasure. Discourses associated with pleasure acted as an important way for older men to examine their bodies and contemplate the significance of hockey in their lives. Through the comradery players developed with each other, their interactions with the material objects of hockey, and their emplacement on hockey rinks and arenas, they found ways to celebrate their bodies as both aging and capable of experiencing pleasure - implicitly challenging neoliberal discourses of old age in the process.

MeSH Terms

-

Keywords

Aging; Embodiment; Emplacement; Hockey; Materialism; Men; Neoliberalism; Pleasure; Risk

The Many Lives of Myc in the Pancreatic β-Cell.

Abstract

Diabetes results from insufficient numbers of functional pancreatic β-cells. Thus, increasing the number of available functional β-cells ex vivo for transplantation, or regenerating them in situ in diabetic patients, is a major focus of diabetes research. The transcription factor, Myc, discovered decades ago, lies at the nexus of most, if not all, known proliferative pathways. Based on this, many studies in the 1990's and early 2000's explored the potential of harnessing Myc expression to expand β-cells for diabetes treatment. Nearly all these studies in β-cells used pathophysiological or supraphysiological levels of Myc and reported enhanced β-cell death, de-differentiation or the formation of insulinomas if co-overexpressed with Bcl-xL, an inhibitor of apoptosis. This obviously reduced the enthusiasm for Myc as a therapeutic target for β-cell regeneration. However, recent studies indicate that "gentle" induction of Myc expression enhances β-cell replication without induction of cell death or loss of insulin secretion, suggesting that appropriate levels of Myc could have therapeutic potential for β-cell regeneration. Furthermore, although it has been known for decades that Myc is induced by glucose in β-cells very little is known about how this essential anabolic transcription factor perceives and responds to nutrients and increased insulin demand in vivo. Here we summarize the previous and recent knowledge of Myc in the β-cell, its potential for β-cell regeneration and its physiological importance for neonatal and adaptive β-cell expansion.

MeSH Terms

-

Keywords

Adaptation; DNA methylation; Myc (c-Myc); aging; beta cell (B-cell); cell proliferation; diabetes; glucose

The effects of everyday-life exposure to polycyclic aromatic hydrocarbons on biological age indicators.

Abstract

Further knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti-benzo[a]pyrene diolepoxide (B[a]PDE-DNA) adducts. The study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and anti-B[a]PDE-DNA by high-performance-liquid-chromatography. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction. Structural equation modelling analysis evaluated these complex relationships. Anti-B[a]PDE-DNA enhanced with PAH exposure (p = 0.005) and active smoking (p = 0.0001), whereas decreased with detoxifying GSTM1 (p = 0.021) and in females (p = 0.0001). Subsequently, LTL and LmtDNAcn reduced with anti-B[a]PDE-DNA (p = 0.028 and p = 0.018), particularly in males (p = 0.006 and p = 0.0001). Only LTL shortened with age (p = 0.001) while elongated with active smoking (p = 0.0001). Besides this, the most significant determinants of PAH exposure that raised anti-B[a]PDE-DNA were indoor and diet (p = 0.0001), the least was outdoor (p = 0.003). New findings stemming from our study suggest that certain preventable everyday life exposures to PAHs reduce LTL and LmtDNAcn. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases. Everyday life exposure to polycyclic aromatic hydrocarbons reduces leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.

MeSH Terms

-

Keywords

Biological aging; DNA adduct; Mitochondrial DNA copy number; Polycyclic aromatic hydrocarbon; Structural equation modelling; Telomere length

A Study on the Influence of Social Leisure Activities on the Progression to the Stage of Frailty in Korean Seniors.

Abstract

In this study, we performed a logistic regression analysis according to the frequency of participation in social leisure activities (education, clubs, social groups, volunteer activities, religious activities, and senior citizens' welfare center use) by men and women aged ≥ 65 years. We investigated the frequency of participation in social leisure activities and their association with the level of frailty (health vs. pre-frailty, health vs. frailty, pre-frailty vs. frailty). This study included 10,297 older adults (men: 4128, women: 6169) who participated in the 2017 National Survey of Older Koreans, and were divided into three groups (healthy, pre-frailty, and frailty). Five frailty index components were used to measure the frailty level. There was a positive relationship between the elderly's religious activities, four times a week, from the healthy stage to the frailty stage, from the healthy stage to the pre-frailty stage, and from the pre-frailty stage to the frailty. In addition, positive associations emerged in leisure activities and club activities, respectively, from the healthy stage to the frailty stage (once a week, respectively). Positive association also emerged from the healthy stage to the pre-frailty and from the pre-frailty stage to the frailty stage (once a month to once in a two-week period).

MeSH Terms

-

Keywords

Korean senior; aging; frailty; national survey; older adults; social leisure activities

Caloric restriction: implications for sarcopenia and potential mechanisms.

Abstract

Sarcopenia is a potential risk factor for weakness, disability and death in elderly individuals. Therefore, seeking effective methods to delay and treat sarcopenia and to improve the quality of life of elderly individuals is a trending topic in geriatrics. Caloric restriction (CR) is currently recognized as an effective means to extend the lifespan and delay the decline in organ function caused by aging. In this review, we describe the effects of CR on improving muscle protein synthesis, delaying muscle atrophy, regulating muscle mitochondrial function, maintaining muscle strength, promoting muscle stem cell (MuSC) regeneration and differentiation, and thus protecting against sarcopenia. We also summarize the possible cellular mechanisms by which CR delays sarcopenia. CR can delay sarcopenia by reducing the generation of oxygen free radicals, reducing oxidative stress damage, enhancing mitochondrial function, improving protein homeostasis, reducing iron overload, increasing autophagy and apoptosis, and reducing inflammation. However, the relationships between CR and genetics, sex, animal strain, regimen duration and energy intake level are complex. Therefore, further study of the proper timing and application method of CR to prevent sarcopenia is highly important for the aging population.

MeSH Terms

-

Keywords

aging; calorie restriction; cellular mechanism; sarcopenia

Food insecurity and T-cell dysregulation in women living with HIV on antiretroviral therapy.

Abstract

Food insecurity is associated with increased morbidity and mortality in people living with HIV on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown. In 241 women participating in the Women's Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and co-stimulation (%CD57- CD28+) on CD4+ and CD8+ T-cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at up to three study visits and adjusting for sociodemographic and clinical factors. At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T-cells, increased senescence of CD8+ T-cells, and decreased co-stimulation of CD4+ and CD8+ T-cells (all p<0.05), adjusting for age, race/ethnicity, income, education, substance use, smoking, HIV viral load, and CD4 cell count. In stratified analyses, the association of food insecurity with CD4+ T-cell activation was more pronounced in women with uncontrolled HIV (viral load >40 copies/mL and CD4 <500 cells/mm 3), but remained statistically significant in those with controlled HIV. Food insecurity may contribute to the persistent immune activation and senescence in women living with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non-AIDS-related disease risk in this population.

MeSH Terms

-

Keywords

HIV; exhaustion; food insecurity; immune activation; senescence

Increased intrinsic excitability and decreased synaptic inhibition in aged somatosensory cortex pyramidal neurons.

Abstract

Sensorimotor performance declines during advanced age, partially due to deficits in somatosensory acuity. Cortical receptive field expansion contributes to somatosensory deficits, suggesting increased excitability or decreased inhibition in primary somatosensory cortex (S1) pyramidal neurons. To ascertain changes in excitability and inhibition, we measured both properties in neurons from vibrissal S1 in brain slices from young and aged mice. Because adapting and non-adapting neurons-the principal pyramidal types in layer 5 (L5)-differ in intrinsic properties and inhibitory inputs, we determined age-dependent changes according to neuron type. We found an age-dependent increase in intrinsic excitability in adapting neurons, caused by a decrease in action potential threshold. Surprisingly, in non-adapting neurons we found both an increase in excitability caused by increased input resistance, and a decrease in synaptic inhibition. Spike frequency adaptation, already small in non-adapting neurons, was further reduced by aging, whereas sag, a manifestation of I , was increased. Therefore, aging caused both decreased inhibition and increased intrinsic excitability, but these effects were specific to pyramidal neuron type.

MeSH Terms

-

Keywords

Action potential threshold; Aging; Barrel cortex; Critical frequency; GABA; Hyperexcitability; Inhibition; Input resistance; Intrinsic excitability; Layer 5; Somatosensory cortex; Spike frequency adaptation; sag

Increased functional connectivity supports language performance in healthy aging despite gray matter loss.

Abstract

Although language is quite preserved from aging, it remains unclear whether age-related differences lead to a deterioration or reorganization in language functional networks, or to different dynamics with other domains (e.g., the multiple-demand system). The present study is aimed at examining language networks, using resting-state functional magnetic resonance imaging in typical aging in relation to language performance. Twenty-three (23) younger adults and 24 healthy older adults were recruited. Volumetric gray matter differences between the 2 groups were assessed using voxel-based morphometry. Then, seed-based analyses, integrated local correlations in core regions of the language network, and within- and between-network connectivity were performed. We expected less extended connectivity maps, local coherence diminution, and higher connectivity with the multiple-demand system in older adults. On the contrary, analyses showed language network differences in healthy aging (i.e., increased connectivity with areas inside and outside language network), but no deterioration, despite widespread atrophy in older adults. Integrated local correlation revealed alterations that were unnoticeable with other analyses. Although gray matter loss was not correlated with language performance, connectivity differences were positively correlated with fluency performance in the older group. These results differ from the literature concerning other cognitive networks in aging in that they show extra internetwork connections without a decrease in intranetwork language connections. This reorganization could explain older adults' good language performance and could be interpreted in accordance with the scaffolding theory of aging and cognition.

MeSH Terms

-

Keywords

Aging; Functional connectivity; Language; Resting-state; fMRI

Development of Energy-Efficient Superhydrophobic Polypropylene Fabric by Oxygen Plasma Etching and Thermal Aging.

Abstract

This study developed a human-friendly energy-efficient superhydrophobic polypropylene (PP) fabric by oxygen plasma etching and short-term thermal aging without additional chemicals. The effect of the microroughness on the superhydrophobicity was examined by adjusting the weave density. After the PP fabric was treated with oxygen plasma etching for 15 min and thermal aging at 120 °C for 1 h (E15H120 1 h), the static contact and shedding angles were 162.7° ± 2.4° and 5.2° ± 0.7° and the energy consumption was 136.4 ± 7.0 Wh. Oxygen plasma etching for 15 min and thermal aging at 120 °C for 24 h (E15H120 24 h) resulted in a static contact and shedding angle of 180.0° ± 0.0° and 1.8° ± 0.2° and energy consumption of 3628.5 ± 82.6 Wh. E15H120 1 h showed a lower shedding angle but had a higher sliding angle of 90°. E15H120 24 h exhibited shedding and sliding angles of less than 10°. Regardless of the thermal aging time, superhydrophobicity was higher in high-density fabrics than in low-density fabrics. The superhydrophobic PP fabric had a similar water vapor transmission rate and air permeability with the untreated PP fabric, and it showed a self-heading property after washing followed by tumble drying and hot pressing.

MeSH Terms

-

Keywords

energy-efficient; plasma etching; polypropylene; self-cleaning; superhydrophobicity; thermal aging; weave density

The Receptor for Advanced Glycation End Product (RAGE) Pathway in COVID-19.

Abstract

Coronavirus disease-2019 (COVID-19) with lung involvement frequently causes morbidity and mortality. Advanced age appears to be the most important risk factor. The receptor for advanced glycation end-product (RAGE) pathway is considered to play important roles in the physiological aging and pathogenesis of lung diseases. This study aims to investigate the possible relationship between COVID-19 and RAGE pathway. This study included 23 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed-tomography. Serum soluble-RAGE (sRAGE) levels were determined using enzyme-linked immunosorbent assay. The sRAGE levels were significantly higher in the asymptomatic group than in the control group. Age, fibrinogen, C-reactive protein, and ferritin levels were higher and the sRAGE level was lower in the patients with lung involvement than in the asymptomatic patients. In the present study, patients with high sRAGE levels were younger and had asymptomatic COVID-19. Patients with low sRAGE levels were elderly patients with lung involvement, which indicates that the RAGE pathway plays an important role in the aggravation of COVID-19.

MeSH Terms

-

Keywords

Aging; COVID-19; Co-morbidity; Infection; Inflammation; The receptor for advanced glycation end product (RAGE)

Impact of an 8-Year Intensive Lifestyle Intervention on an Index of Multimorbidity.

Abstract

Type 2 diabetes mellitus and obesity are sometimes described as conditions that accelerate aging. Multidomain lifestyle interventions have shown promise to slow the accumulation of age-related diseases, a hallmark of aging. However, they have not been assessed among at-risk individuals with these two conditions. We examined the relative impact of 8 years of a multidomain lifestyle intervention on an index of multimorbidity. Randomized controlled clinical trial comparing an intensive lifestyle intervention (ILI) that targeted weight loss through caloric restriction and increased physical activity with a control condition of diabetes support and education (DSE). Sixteen U.S. academic centers. A total of 5,145 volunteers, aged 45 to 76, with established type 2 diabetes mellitus and overweight or obesity who met eligibility criteria for a randomized controlled clinical trial. A multimorbidity index that included nine age-related chronic diseases and death was tracked over 8 years of intervention delivery. Among individuals assigned to DSE, the multimorbidity index scores increased by an average of .98 (95% confidence interval [CI] = .94-1.02) over 8 years, compared with .89 (95% CI = .85-.93) among those in the multidomain ILI, which was a 9% difference (P = .003). Relative intervention effects were similar among individuals grouped by baseline body mass index, age, and sex, and they were greater for those with lower levels of multimorbidity index scores at baseline. Increases in multimorbidity over time among adults with overweight or obesity and type 2 diabetes mellitus may be slowed by multidomain ILI. J Am Geriatr Soc 68:2249-2256, 2020.

MeSH Terms

-

Keywords

aging; multidomain intervention; obesity; type 2 diabetes mellitus

Longitudinal profiling of the blood transcriptome in an African green monkey aging model.

Abstract

African green monkeys (AGMs, [i]Chlorocebus aethiops[/i]) are Old World monkeys which are used as experimental models in biomedical research. Recent technological advances in next generation sequencing are useful for unraveling the genetic mechanisms underlying senescence, aging, and age-related disease. To elucidate the normal aging mechanisms in older age, the blood transcriptomes of nine healthy, aged AGMs (15‒23 years old), were analyzed over two years. We identified 910‒1399 accumulated differentially expressed genes (DEGs) in each individual, which increased with age. Aging-related DEGs were sorted across the three time points. A major proportion of the aging-related DEGs belonged to gene ontology (GO) categories involved in translation and rRNA metabolic processes. Next, we sorted common aging-related DEGs across three time points over two years. Common aging-related DEGs belonged to GO categories involved in translation, cellular component biogenesis, rRNA metabolic processes, cellular component organization, biogenesis, and RNA metabolic processes. Furthermore, we identified 29 candidate aging genes that were upregulated across the time series analysis. These candidate aging genes were linked to protein synthesis. This study describes a changing gene expression pattern in AGMs during aging using longitudinal transcriptome sequencing. The candidate aging genes identified here may be potential targets for the treatment of aging.

MeSH Terms

-

Keywords

African green monkey; aging; aging candidate gene; longitudinal transcriptome

Age-related gene expression changes in lumbar spinal cord: Implications for neuropathic pain.

Abstract

Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24-32 months) versus young mice (2-4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.

MeSH Terms

-

Keywords

Cxcl13; Dorsal horn; ageing; aging; astrocytes; chemokines; glia; inflammation; microglia

Lignin-derived phenolic compounds in cachaça aged in new barrels made from two oak species.

Abstract

Aging cachaça in wooden barrels is essential to improve its quality. The level of maturation of distillates can be determined based on the contents of aging-marker phenolic compounds extracted from the lignin of the wooden barrel. This study aimed to characterize the aging process of cachaça by analyzing the mechanism of lignin degradation during its maturation in new barrels made from two oak species, European ([i]Quercus petraea[/i]) and American ([i]Quercus alba[/i]), for up to 60 months. Evaluation was based on the analyses of cinnamic aldehydes (sinapaldehyde and coniferaldehyde), benzoic aldehydes (syringaldehyde and vanillin), and benzoic acids (syringic and vanillic acids) using high-performance liquid chromatography. Oak species had a significant effect on all the studied phenolic compounds. Higher contents of all the identified phenolic compounds were found in cachaça aged in barrels made from American oak. The total contents of benzoic acids (vanillic and syringic acids) can be considered for predicting the level of maturation of cachaça aged in barrels made from both oak species. Based on the composition of maturation-related congeners, it is likely that for cachaça each year of aging in new oak barrels corresponds to approximately 5 years of aging for spirits in general commercialized worldwide.

MeSH Terms

-

Keywords

Aging; Food analysis; Food technology; Lignin; Oak species; Phenolic compounds; Sugarcane spirit

Depresión en el adulto mayor intervenido quirúrgicamente.

Abstract

To determine the degree of depression in elderly adults after surgery and its relation with the duration of anesthesia. We conducted an observational, comparative, prospective and longitudinal study. We included 73 elderly adults aged 60 scheduled for different surgical procedures. Their degree of depression was evaluated prior to and after the surgery with the short version of the Yasavage Geriatric Depression Scale. They were classified according to the score: no depression (0-5), mild depression (6-9) and established depression (10-15). The relation of depression with anesthesia duration was determined. The sample size was calculated for proportions. Descriptive statistics were used as well as χ (p < 0.05). In the first evaluation 47 patients (64%) were not depressed, 21 (29%) had mild depression and 5 (7%) had established depression. In the second evaluation, we found that 44 patients (60%) were not depressed, 21 (29%) had mild depression and 8 (11%) had established depression. The relation between depression and anesthesia duration was χ = 0.81. We did not establish a relation between depression and anesthesia duration in surgically intervened elderly adults.

MeSH Terms

-

Keywords

Adult; Adulto; Aging; Anestesia; Anesthesia; Depresión; Depression; Envejecimiento; Espinal; Spinal

A systematic review of psychosocial interventions for older adults living with HIV.

Abstract

The rapidly growing segment of older adults living with HIV faces unique set of psychosocial challenges that may differ from their younger counterparts. The objective of this review is to systematically examine current published literature on interventions designed to improve the psychosocial wellbeing of older adults living with HIV. A pre-specified search strategy was applied to four databases: PubMed, CINAHL Plus with Text, PsycINFO, and Health Source. Authors reviewed published studies on psychosocial interventions for older adults with HIV and reported psychosocial variables as primary outcomes of the interventions. The final review included nine intervention studies. Psychosocial outcomes measured across multiple studies included depression, quality of life, social support, cognitive functioning, and coping skills. Some studies also measured physical activity, HIV-related discrimination, lack of affordable housing, and access to substance abuse treatment. Our study suggests a paucity of psychosocial intervention research on adults aging with HIV. This review suggests that most psychosocial interventions had small to moderate effects in improving the psychosocial wellbeing of older people living with HIV. Findings highlight the need for clinical, community, and home-based interventions to ensure that individuals can achieve a higher quality of life while aging with HIV.

MeSH Terms

-

Keywords

Aging; Depression; HIV; Older adults; Psychosocial intervention; Stress

Comparison of the Effects of KE and AED Peptides on Functional Activity of Human Skin Fibroblasts during Their Replicative Aging.

Abstract

We studied the effect of KE and AED peptides on the expression of sirtuin-1, sirtuin-6, collagen I, cytokines (IL-1, TGF-β), and transcription factor NF-κB in human skin fibroblasts during their replicative aging. Immunocytochemical analysis and confocal microscopy showed that KE peptide reduces the synthesis of factors of the inflammatory response IL-1, NF-κB, and TGF-β and stimulates the synthesis of sirtuin-6. KE peptide normalizes the immunological function of human skin fibroblasts during their aging. AED peptide activates the synthesis of sirtuin-1, sirtuin-6, and collagen I in human skin fibroblasts during their replicative aging, which attests to its geroprotective effect.

MeSH Terms

-

Keywords

collagen I; human skin fibroblasts; replicative aging; short peptides; sirtuins

Genetic defects in the sphingolipid degradation pathway and their effects on microglia in neurodegenerative disease.

Abstract

Sphingolipids, which function as plasma membrane lipids and signaling molecules, are highly enriched in neuronal and myelin membranes in the nervous system. They are degraded in lysosomes by a defined sequence of enzymatic steps. In the related group of disorders, the sphingolipidoses, mutations in the genes that encode the individual degradative enzymes cause lysosomal accumulation of sphingolipids and often result in severe neurodegenerative disease. Here we review the information indicating that microglia, which actively clear sphingolipid-rich membranes in the brain during development and homeostasis, are directly affected by these mutations and promote neurodegeneration in the sphingolipidoses. We also identify parallels between the sphingolipidoses and more common forms of neurodegeneration, which both exhibit evidence of defective sphingolipid clearance in the nervous system.

MeSH Terms

-

Keywords

Aging; Alzheimer's disease; Microglia; Parkinson's disease; Sphingolipidoses; Sphingolipids

Multifaceted role of extracellular vesicles in atherosclerosis.

Abstract

Extracellular vesicles (EVs) are small vesicles released by the majority of cells in response to cell activation or death stimuli. They are grouped as small EVs or exosomes, large EVs such as microvesicles (MVs) and apoptotic bodies, resulting from distinct mechanisms of generation. EVs are released into the extracellular space, in most human biological fluids and tissues, including atherosclerotic plaques. They transport complex cargo of bioactive molecules, including proteins, lipids and genetic material and are therefore involved in pathophysiological pathways of cell-cell communication. Indeed, EVs are involved in several processes such as inflammation, coagulation, vascular dysfunction, angiogenesis and senescence, contributing to the initiation and progression of atherothrombotic diseases. Consequently, they behave as a determinant of atherosclerotic plaque vulnerability leading to major cardiovascular disorders. Over the last decade, the field of EVs research has grown, highlighting their involvement in atherosclerosis. However, limitations in both detection methodologies and standardisation have hindered implementation of EVs in the clinical settings. This review summarizes the effect of EVs in atherosclerosis development, progression and severity, with specific attention devoted to their ambivalent roles in senescence and hemostasis. This review will also highlight the role of MVs as multifaceted messengers, able to promote or to attenuate atherosclerosis progression. Finally, we will discuss the main technical challenges and prerequisites of standardization for driving EVs to the clinics and delineate their relevance as emergent biomarkers and innovative therapeutic approaches in atherosclerosis.

MeSH Terms

-

Keywords

Atherosclerosis; Biomarkers; Extracellular vesicles; Hemostasis; Senescence

The association between prenatal exposure to thallium and shortened telomere length of newborns.

Abstract

Thallium is a widely known toxic heavy metal that has been reported have embryo toxicity. We aimed to investigate the relationship of prenatal thallium exposure with neonatal telomere length. A total of 746 mother-newborn pairs were recruited from Wuhan Children Hospital between November 2013 and March 2015 in Wuhan City, China. Maternal thallium exposure levels were measured in spot urine samples collected during the three trimesters and during hospital delivery using inductively coupled plasma mass spectrometry. Neonatal relative telomere length (rTL) was measured by a real-time quantitative polymerase chain reaction assay in cord blood. Multiple informant models were used to evaluate the association of maternal thallium exposure with neonatal rTL. After adjustment for multiple potential confounders, each 25% incremental increase of maternal thallium exposure, measured in urine samples collected during hospital delivery, was associated with a 1.85% shortened neonatal rTL (95% CI: -3.62%, -0.05%; P = 0.044). Similarly, mothers in the highest quartile of urinary thallium exposure had a 11.74% (95% CI: -21.57%, -0.68%; P = 0.038) shorter cord blood leukocyte rTL than those in the lowest quartile. However, no significant association was found between neonatal rTL and maternal thallium exposure measured in urine samples collected during the three trimesters of pregnancy. This study reveals that prenatal thallium exposure was related to shortened neonatal telomere length in Chinese population, pointing to the important role of thallium exposure in accelerating biological aging.

MeSH Terms

-

Keywords

Biological aging; Cord blood; Telomere length; Thallium

[i]FOXO3[/i] longevity genotype mitigates the increased mortality risk in men with a cardiometabolic disease.

Abstract

[i]FOXO3[/i] is a prominent longevity gene. To date, no-one has examined whether longevity-associated [i]FOXO3[/i] genetic variants protect against mortality in all individuals, or only in those with aging-related diseases. We therefore tested longevity-associated [i]FOXO3[/i] single nucleotide polymorphisms in a haplotype block for association with mortality in 3,584 elderly American men of Japanese ancestry, 2,512 with and 1,072 without a cardiometabolic disease (CMD). At baseline (1991-1993), 1,010 CMD subjects had diabetes, 1,919 had hypertension, and 738 had coronary heart disease (CHD). Follow-up until Dec 31, 2019 found that in CMD-affected individuals, longevity-associated alleles of [i]FOXO3[/i] were associated with significantly longer lifespan: haplotype hazard ratio 0.81 (95% CI 0.72-0.91; diabetes 0.77, hypertension 0.82, CHD 0.83). Overall, men with a CMD had higher mortality than men without a CMD ([i]P[/i]=6x10 ). However, those men with a CMD who had the [i]FOXO3[/i] longevity genotype had similar survival as men without a CMD. In men without a CMD there was no association of longevity-associated alleles of [i]FOXO3[/i] with lifespan. Our study provides novel insights into the basis for the long-established role of [i]FOXO3[/i] as a longevity gene. We suggest that the [i]FOXO3[/i] longevity genotype increases lifespan only in at-risk individuals by protection against cardiometabolic stress.

MeSH Terms

-

Keywords

FOXO3; genetics; longevity; mortality; resilience

Identification of genes associated with endometrial cell aging.

Abstract

Aging of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine aging are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine aging. Gene expression patterns were assessed by two RNA sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5 and 8 week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20 s and 40 s (10 cases each). In the secretory phase samples, 3,3'- diaminobenzidine (DAB) staining intensities of IL17RB, CXCL12 and CXCL14 for patients in their 40 s were significantly higher than that for patients in their 20 s, as detected by a Mann Whitney U test. These results suggest that these genes are candidate markers for endometrial aging and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.

MeSH Terms

-

Keywords

CXCL12; CXCL14; IL17RB; endometrial cell aging; infertility; quantitative immunohistochemistry

Cognitive decline negatively impacts physical function.

Abstract

Many older adults report difficulty performing one or more activities of daily living. These difficulties may be attributed to cognitive decline and as a result, measuring cognitive status among aging adults may help provide an understanding of current functional status. The purpose of the present investigation was to determine the association between cognitive status and measures of physical functioning. Seventy-six older adults participated in this study; 41 were categorized as normal memory function (NM) and 35 were poor memory function (PM). NM participants had significantly higher physical function as measured by Short Physical Performance Battery (SPPB; 9.4 ± 2.2 vs. 8.4 ± 2.0; p = .03) and peak velocity (0.67 ± 0.16 vs. 0.56 ± 0.19; p = .04) during a quick sit-to-stand task. Dual-task walking velocities were 22% and 126% slower between cognitive groups for the fast and habitual trials, respectively when compared to the single-task walking condition. Significant correlations existed between measures of memory and physical function. The largest correlations with memory were for peak (r = 0.42) and average (r = 0.38) velocity. The results suggest a positive relationship between physical function and cognitive status. However, further research is needed to determine the mechanism of the underlying relationships between physical and cognitive function.

MeSH Terms

-

Keywords

Aging; Cognition, movement velocity, dual-task, memory; Physical function

Changes in self-estimated step-over ability among older adults: A 3-year follow-up study.

Abstract

There is a growing body of literature examining age-related overestimation of one's own physical ability, which is a potential risk of falls in older adults, but it is unclear what leads them to overestimate. This study aimed to examine 3-year longitudinal changes in self-estimated step-over ability, along with one key risk factor: low frequency of going outdoors (FG), which is a measure of poor daily physical activity. This cohort study included 116 community-dwelling older adults who participated in baseline and 3-year follow-up assessments. The step-over test was used to measure both the self-estimated step-over bar height (EH) and the actual bar height (AH). Low FG was defined as going outdoors either every few days or less at baseline. The number of participants who overestimated their step-over ability (EH>AH) significantly increased from 10.3% to 22.4% over the study period. AH was significantly lower at follow-up than at baseline in both participants with low and high FGs. Conversely, among participants with low FG, EH was significantly higher at follow-up than at baseline, resulting in increased self-estimation error toward overestimation. Regression model showed that low FG was independently associated with increased error in estimation (i.e., tendency to overestimate) at follow-up. The present study indicated that self-overestimated physical ability in older adults is not only due to decreased physical ability but also due to increased self-estimation of one's ability as a function of low FG. Active lifestyle may be critical for maintaining accurate estimations of one's own physical ability.

MeSH Terms

-

Keywords

Aging; Inactive lifestyle; Judgment; Self-assessment; Step over

Improvements of Disability Outcomes in CAPABLE Older Adults Differ by Financial Strain Status.

Abstract

The Community Aging in Place-Advancing Better Living for Elders (CAPABLE) program reduces disability in low-income older adults. In this study, we used CAPABLE baseline and 5-month data to examine whether its effects in reducing activities of daily living (ADLs) and instrumental ADLs (IADLs) difficulties differed by participants' financial strain status. At baseline, participants with financial strain were more likely to report higher scores on depression ([i]p[/i] < .001), have low energy ([i]p[/i] < .001), and usually feel tired ([i]p[/i] = .004) compared with participants without financial strain, but did not differ in ADL/IADL scores. Participants with financial strain benefited from the program in reducing ADL (relative risk [RR]: 0.61, 95% confidence interval [CI]: 0.43, 0.86) and IADL disabilities (RR: 0.69, 95% CI: 0.54, 0.87), compared with those with financial strain receiving attention control. Individuals with financial strain benefited more from a home-based intervention on measures of disability than those without financial strain. Interventions that improve disability may be beneficial for financially strained older adults.

MeSH Terms

-

Keywords

aging; health disparity; intervention; physical function

Body Size and Cuticular Hydrocarbons as Larval Age Indicators in the Forensic Blow Fly, Chrysomya albiceps (Diptera: Calliphoridae).

Abstract

Chrysomya albiceps (Wiedemann 1819) is one of the most important insects in forensic entomology. Its larval developmental and survival rates are influenced by nutritional resources, temperature, humidity, and geographical regions. The present study investigated the possibility of relying on body size and cuticular hydrocarbon composition as indicators for age estimation of the different larval instars of C. albiceps. Larvae were maintained in standardized laboratory conditions at different experimental temperatures. All larval instars (first, second, and third) were randomly collected for measuring their body sizes and for estimating their cuticular hydrocarbons at different rearing temperatures (30, 35, 40, and 45°C) using gas chromatography-mass spectrometry (GC-MS). Results indicated that the duration of larval stage was temperature dependent as it gradually decreased on increasing the rearing temperature (30, 35, and 40°C) except 45°C at which larval development was ceased. In contrary, larval body size, in terms of length, width, and weight, was temperature dependent as it gradually increased with larval development on increasing rearing temperature except at 45°C at which larval development was ceased. The GC-MS showed a significant difference in the extracted components of cuticular hydrocarbons between different larval instars reared in the same temperature and between the same larval instar that reared at different temperatures. Furthermore, the highest and lowest amounts of cuticular hydrocarbons were detected at 35 and 40°C, respectively. Overall, larval body size and cuticular hydrocarbon components were temperature dependent within the range 30-40°C, which may suggest them as possible reliable age indicators for estimating the postmortem interval in the field of medicolegal entomology.

MeSH Terms

-

Keywords

         Chrysomya albiceps
       ; body size; cuticular hydrocarbon; forensic; larval longevity

Machine Learning of Hematopoietic Stem Cell Divisions from Paired Daughter Cell Expression Profiles Reveals Effects of Aging on Self-Renewal.

Abstract

Changes in stem cell activity may underpin aging. However, these changes are not completely understood. Here, we combined single-cell profiling with machine learning and in vivo functional studies to explore how hematopoietic stem cell (HSC) divisions patterns evolve with age. We first trained an artificial neural network (ANN) to accurately identify cell types in the hematopoietic hierarchy and predict their age from single-cell gene-expression patterns. We then used this ANN to compare identities of daughter cells immediately after HSC divisions and found that the self-renewal ability of individual HSCs declines with age. Furthermore, while HSC cell divisions are deterministic and intrinsically regulated in young and old age, they are variable and niche sensitive in mid-life. These results indicate that the balance between intrinsic and extrinsic regulation of stem cell activity alters substantially with age and help explain why stem cell numbers increase through life, yet regenerative potency declines.

MeSH Terms

-

Keywords

aging; artificial neural network; hematopoietic stem cell; machine learning; self-renewal

Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation.

Abstract

The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and P2RY12. In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. We demonstrate that Tmem119 and P2RY12 expression is evident within both CD45 and CD45 myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and P2RY12, making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the "infiltrating myeloid" population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies.

MeSH Terms

-

Keywords

Aging; Brain infiltrating myeloid cells; CD45; Cerebral amyloid angiopathy; Microglia; Neuroinflammation; P2RY12; Stroke; Tmem119

Laying the foundation for an International Classification of Functioning, Disability and Health Core Set for community-dwelling elderly adults in primary care: the clinical perspective identified in a cross-sectional study.

Abstract

Having more information about the biopsychosocial functioning of their geriatric patients might help physicians better balance medical interventions according to patients' needs. For this reason, we aimed to develop an easy-to-handle International Classification of Functioning, Disability and Health (ICF) Core Set for community-dwelling geriatric patients aged 75 and older in primary care. In this empirical study, we describe the functioning and health of community-dwelling patients aged 75 and older in primary care in Germany and identify the most common problems encountered by these individuals when using the ICF. In this exploratory, cross-sectional study, a health professional conducted semi-structured interviews. Community-dwelling older adults aged 75 and older in Germany. 65 participants (mean age=80.2, SD=3.6). Extended ICF Checklist V.2.1a, patients prioritised chapters of the 'activities and participation' component. The three most common impairments for 'body functions' were [i]visual system functions[/i] (ICF-code [i]b210[/i]; 89%), [i]blood pressure functions[/i] ([i]b420[/i]; 80%) and [i]sensations associated with hearing and vestibular functions[/i] ([i]b240; 59%[/i]). For 'body structures', they were [i]eyes, ears and related structures[/i] ([i]s2[/i]; 81%), [i]structure of mouth[/i] ([i]s320[/i]; 74%) and [i]structures related to the digestive, metabolic and endocrine systems[/i] ([i]s5[/i]; 49%). For the 'activities and participation' component, adequate aids compensated for activity limitations to a certain degree. Still, after having adequate aids, the category in which the participants had the most difficulty was [i]walking[/i] ([i]d450;[/i] 35%). Participants rated the 'mobility' chapter as the most important of all chapters. 'Environmental factors' were facilitators of participants' functioning. This empirical study provides a list of ICF categories relevant to older adults from the clinical perspective. Along with lists from the other three preparatory studies, it will form the basis for the development of an ICF Core Set for community-dwelling older adults in primary care. The trial is registered in ClinicalTrials.gov (NCT03384732).

MeSH Terms

-

Keywords

ICF; aging; community-dwelling older people; core set; functioning; general practice

Histone Variant H2A.J Marks Persistent DNA Damage and Triggers the Secretory Phenotype in Radiation-Induced Senescence.

Abstract

Irreparable double-strand breaks (DSBs) in response to ionizing radiation (IR) trigger prolonged DNA damage response (DDR) and induce premature senescence. Profound chromatin reorganization with formation of senescence-associated heterochromatin foci (SAHF) is an essential epigenetic mechanism for controlling the senescence-associated secretory phenotype (SASP). To decipher molecular mechanisms provoking continuous DDR leading to premature senescence, radiation-induced DSBs (53BP1-foci) and dynamics of histone variant H2A.J incorporation were analyzed together with chromatin re-modeling in human fibroblasts after IR exposure. High-resolution imaging by transmission electron microscopy revealed that persisting 53BP1-foci developed into DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), consistently located at the periphery of SAHFs. Quantitative immunogold-analysis by electron microscopy revealed that H2A.J, steadily co-localizing with 53BP1, is increasingly incorporated into DNA-SCARS during senescence progression. Strikingly, shRNA-mediated H2A.J depletion in fibroblasts modified senescence-associated chromatin re-structuring and abolished SASP, thereby shutting down the production of inflammatory mediators. These findings provide mechanistic insights into biological phenomena of SASP and suggest that H2A.J inhibition could ablate SASP, without affecting the senescence-associated growth arrest.

MeSH Terms

-

Keywords

DNA-SCARS; histone variant H2A.J; radiation-induced senescence; senescence-associated heterochromatin foci (SAHF); senescence-associated secretory phenotype (SASP); transmission electron microscopy (TEM)

TRIM27 Functions as a Novel Oncogene in Non-Triple-Negative Breast Cancer by Blocking Cellular Senescence through p21 Ubiquitination.

Abstract

In the current study, we aimed to explore the correlation between TRIM27 and breast cancer prognosis, as well as the functions of TRIM27 in breast cancer and their underlying mechanisms. Bioinformatics analyses were used to examine the correlation between TRIM27 and breast cancer prognosis. Moreover, TRIM27 knockdown and overexpression in breast cancer cells were performed to investigate its functions in breast cancer. Tamoxifen (TAM) was applied to evaluate the influence of TRIM27 on chemoresistance of breast cancer cells, while co-immunoprecipitation (coIP) was performed to identify the E3 ubiquitin ligase capability of TRIM27. High expression of TRIM27 was found in non-triple-negative breast cancer (non-TNBC) tumor tissues and was positively correlated with the mortality of non-TNBC patients. Moreover, TRIM27 could suppress non-TNBC cell apoptosis and senescence, promote cell viability and tumor growth, counteract the anti-cancer effects of TAM, and mediate ubiquitination of p21. In addition, EP300 could enhance the expression of TRIM27 and its transcription promoter H3K27ac. TRIM27, through ubiquitination of p21, might serve as a prognostic biomarker for non-TNBC prognosis. TRIM27 functions as a novel oncogene in non-TNBC cellular processes, especially suppressing cell senescence and interfering with non-TNBC chemoresistance.

MeSH Terms

-

Keywords

EP300; TRIM27; breast cancer; cell apoptosis; cell senescence; chemoresistance; p21; prognosis; transcription; ubiquitination

The Effect of Chronic Diseases on the Use of Health Technology and Digital Services in the Elderly Population in Finland.

Abstract

Digital services are growing in the health-care field. The population in Europe is aging, and digital services are on the rise. There are also plenty of new health-care devices on the market. The aim of this study was to survey how elderly people cope with digital services or devices, especially if they are chronically ill. This quantitative study focuses on the impact of chronic diseases on the use of health technology and digital services. The target group of this study is Finnish people aged 65 or over. Based on the results, a chronic disease or disability is not an obstacle to the use of digital services or health-care technology in the Finnish elderly population. The main obstacles to the use of health technology or digital services are complexity, obscure text, or small font size. According to this study, elderly people seem to trust the device or application. Devices, applications, and online services should be designed so that elderly people's diseases or ability to function are considered.

MeSH Terms

Aged

• Aging
• Biomedical Technology
• Chronic Disease
• Europe
• Finland
• Humans

Keywords

Digital services; Disease; Health care; Health technology

Aging Narratives over 210 years (1810-2019).

Abstract

The World Health Organization launched a recent global campaign to combat ageism, citing its ubiquity and insidious threat to health. The historical context that promoted this pernicious threat is understudied, and such studies lay the critical foundation for designing societal-level campaigns to combat it. We analyzed the trend and content of aging narratives over 210 years across multiple genres-newspaper, magazines, fiction, non-fiction books; and modelled the predictors of the observed trend. A 600-million-word-dataset was created from the Corpus-of-Historical-American-English and the Corpus-of-Contemporary-American-English to form the largest structured historical corpus with over 150,000 texts from multiple genres. Computational linguistics and statistical techniques were applied to study the trend, content, and predictors of aging narratives. Aging narratives have become more negative, in a linear fashion (p=.003), over 210 years. There are distinct shifts: From uplifting narratives of heroism and kinship in the 1800s to darker tones of illness, death, and burden in the 1900s across newspapers, magazines, and non-fiction books. Fiction defied this trend by portraying older adults positively through romantic courtship and war heroism. Significant predictors of ageism over 210 years are the medicalization of aging, loss of status, warmth, competence, and social ostracism. Though it is unrealistic to reverse the course of ageism, its declining trajectory can be ameliorated. Our unprecedented study lay the groundwork for a societal level campaign to tackle ageism. The need to act is more pressing given the Covid-19 pandemic where older adults are constantly portrayed as vulnerable.

MeSH Terms

-

Keywords

Ageism; age discrimination; age stereotypes; historical analysis; media portrayals of aging; medicalization of aging; psychomics; social gerontology; social ostracism

Premature CD4 T Cells Senescence Induced by Chronic Infection in Patients with Acute Coronary Syndrome.

Abstract

Acquired immune responses mediated by CD4 T cells contribute to the initiation and progression of acute coronary syndrome (ACS). ACS patients show acquired immune system abnormalities that resemble the characteristics of autoimmune dysfunction described in the elderly. This study aimed to investigate the role of premature CD4 T cells senescence in ACS and the underlying mechanism. We compared the immunological status of 25 ACS patients, 15 young healthy individuals (C1), and 20 elderly individuals with absence of ACS (C2). The percentages of CD4 T lymphocyte subsets (including naïve, regulatory, memory and effector T cells) in peripheral blood were analyzed. In ACS patients, a significant expansion of CD4 CD28 effector T cells and a decline of CD4 CD25 CD62L Treg cells were observed. In addition, patients with ACS showed an accelerated loss of CD4 CD45RA CD62L naïve T cells and a compensatory increase in the number of CD4 CD45RO memory T cells. ACS patients demonstrated no significant difference in frequency of T cell receptor excision circles (TRECs) compared to age-matched healthy volunteers. The expression of p16 was increased while CD62L was decreased in CD4 CD28 T cells of ACS patients. Compared to healthy donors, ACS patients demonstrated the lowest telomerase activity in both CD4 CD28 and CD4 CD28 T cells. The serum levels of C-reactive protein, Cytomegalovirus IgG, [i]Helicobactor pylori[/i] IgG and [i]Chlamydia pneumonia[/i] IgG were significantly higher in ACS patients. The results suggested that the percentage of CD4 T cell subpopulations correlated with chronic infection, which contributes to immunosenescence. In conclusion, chronic infection induced senescence of premature CD4 T cells, which may be responsible for the development of ACS.

MeSH Terms

-

Keywords

CD28null T cells; CD4+ T cells; acute coronary syndrome; immunosenescence; infection

Autoantibodies specific for C1q, C3b, β2-glycoprotein 1 and annexins may amplify complement activity and reduce apoptosis-mediated immune suppression.

Abstract

Neoplastic cells hijack cell death pathways to evade the immune response. Phosphatidylserine, a marker of apoptotic cells, and its highly conserved bridging proteins, annexins and β2-glycoprotein I, facilitate the efficient removal of apoptotic and necrotic cells via tumor-associated phagocytes in a process called efferocytosis. Efferocytosis results in the clearance of dead and dying cells and local immune suppression. Neoplastic cells also have an increased capacity to activate complement. Complement may facilitate the silent removal of tumor cells and has a dual role in promoting and inhibiting tumor growth. Here I hypothesize that immune response-generating IgG autoantibodies that recognize opsonizing fragments C1q, C3b, and phosphatidylserine-binding proteins (annexins, β2-glycoprotein I) may reduce tumor growth. I propose that these autoantibodies induce a pro-inflammatory, cytotoxic tumor microenvironment. Further, I predict that autoantibodies can drive neoplastic cell phagocytosis in an Fc receptor-dependent manner and recruit additional complement, resulting in immune-stimulatory effects. Excessive complement activation and antibody-dependent cytotoxicity may stimulate anti-tumor responses, including damage to tumor vasculature. Here I provide insights that may aid the development of more effective therapeutic modalities to control cancer. Such therapeutic approaches should kill neoplastic cells and target their interaction with host immune cells. Thereby the pro-tumorigenic effect of dead cancer cells could be limited while inducing the anti-tumor potential of tumor-associated phagocytes.

MeSH Terms

-

Keywords

Aging; Annexin(s); Apoptosis; Autoantibody (-bodies); C1q; C3b; Cancer(s); Complement; Cytotoxicity; Efferocytosis; Immune-suppression/immunosuppression; Lymphoma(s); Necrosis; Phagocytosis; Phosphatidylserine; Tumor(s); Vasculature; b2-glycoprotein 1; b2-glycoprotein I; β2-glycoprotein 1; β2-glycoprotein I

Comparison study of patient demographics and risk factors for surgical site infections following open reduction and internal fixation for lateral malleolar ankle fractures within the medicare population.

Abstract

The purpose of this study was to analyze a comprehensive database to 1) compare patient demographic profiles; and 2) identify patient-related risk factors for surgical site infections (SSIs) following open reduction and internal fixation (ORIF) for lateral malleolar ankle fractures. Patients treated with ORIF for lateral malleolar ankle fractures that developed SSIs within 1-year following the procedure were identified. Study group demographics were compared to a control cohort and risks for developing SSI were calculated using multivariate logistic regression analysis. There were statistically significant differences between the control group and patients with SSIs. The study showed that morbidly obese patients, peripheral vascular disease, and electrolyte/fluid imbalance were the greatest risk factors for developing SSIs following ORIF for lateral malleolar fractures. The study is useful as it can allow orthopaedists to optimize these high-risk patients to potentially mitigate this adverse event.

MeSH Terms

-

Keywords

Geriatrics; Lateral malleolar ankle fracture; Medicare; Outcomes; Risk factors; Surgical site infections

Rapamycin Eyedrops Increased CD4 Foxp3 Cells and Prevented Goblet Cell Loss in the Aged Ocular Surface.

Abstract

Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident ([i]IFN-γ[/i], [i]IL-12[/i], [i]CIITA[/i] and [i]Ctss[/i]); this was accompanied by slightly diminished [i]Unc-51 Like Autophagy Activating Kinase 1[/i] ([i]ULK1[/i]) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45 CD4 Foxp3 cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.

MeSH Terms

-

Keywords

aging; dry eye; goblet cell; inflammation; lacrimal gland; ocular surface; rapamycin

A CTSA-based consultation service to advance research on special and underserved populations.

Abstract

In this report, we describe the implementation and short-term outcomes of a Special Populations Consultation Service within the University of California, Los Angeles (UCLA) Clinical and Translational Science Institute (CTSI). With the goal of increasing the quality and quantity of special population (SP) research, the UCLA CTSI Integrating Special Populations program designed a consultation service to support faculty and trainees conducting research involving one of three CTSI "special populations:" children, older adults, and/or minority; underserved; or health disparity populations. The Special Populations Consultation Service offers three types of activities: grant proposal studios, career consultations, and project reviews. UCLA CTSI faculty with appropriate content expertise serve as consultants. We evaluated this consultation model using satisfaction surveys and by quantifying funded grants and reported changes in career goals in SP research. Between 2016 and 2019, the Special Populations Consultation Service provided 59 consultations including 42 grant studios and was used by researchers at all levels from all four UCLA CTSI institutions. Recipients rated the consultations very highly. Funding success rates were 57% following K-level grant studios and 28% following R-level grant studios. Users of project and career consultations commonly attributed career accomplishments in part to their consultation experiences. The SP Consultation Service is feasible and acceptable and appears to enhance careers of investigators studying special populations.

MeSH Terms

-

Keywords

faculty development; geriatrics; grant review; grant studio; pediatrics; peer review; research consultation service; special populations; underrepresented minorities

Age relationships with telomere length, body weight and body length in wild dugong ([i]Dugong dugon[/i]).

Abstract

The ability to estimate age and determine the growth status of free-ranging dugongs ([i]Dugong dugon[/i]) is vital to providing insight into the basic biology of this endangered species. Currently, age estimation in dugong carcasses relies on counting dentin growth layer groups (GLGs) in tusks, but a disadvantage is they need to be intact. We explored whether measures of telomere length could be used as an alternative approach to age estimation in dugongs given that in other species, telomere length and age are inversely related. In this study, relative telomere length (rTL) was measured by qPCR in skin samples from 24 dugongs of varying ages determined by counts of GLGs. In addition, relationships between age by GLG counts and body weight and length and were examined. Our findings indicate that age estimated by GLGs was negatively correlated with telomere length using the logistic formula with a rate of telomere attrition of approximately 0.036 rTL/year between the ages of 5-20 years. By comparison, both body weight and length were positively correlated with GLG-based age, with growth rates of ~8.8 kg/year for weight and ~3.58 cm/year for length, respectively. After that, growth rates slowed substantially and then plateaued. The results suggest that physical maturity in dugongs occurs at 20 years of age and that measures of rTL might serve as a tool for age estimation in dugongs, living and deceased.

MeSH Terms

-

Keywords

Age; Growth; Senescence; Sirenia; Telomere; Tusk

Palliative and end of life care for people with advanced dementia.

Abstract

Despite growing understanding in recent years of the biological, psychological, social, environmental and spiritual aspects of dementia, people with advanced dementia continue to experience inequalities in accessing healthcare capable of improving their lives. The complexities of advanced dementia challenge professional competence and demand the highest level of skilled, compassionate care. This article, the last in a series on living with advanced dementia, considers the status and direction of palliative care as it applies to people with dementia and explores contemporary issues regarding advanced dementia and end of life, with a focus on guidance for practitioners and support for best practice. It identifies that open communication, clear information and a person-centred approach adopted as early as possible in the syndrome can make this period less distressing. Crucially, people at the end of life should be offered care in line with best practice in palliative and end of life approaches.

MeSH Terms

-

Keywords

advanced dementia; clinical; dementia; end of life care; gerontology; neurology; older people; palliative care

Statin Treatment in Specific Patient Groups: Role for Improved Cardiovascular Risk Markers.

Abstract

Ample evidence supports the use of statin therapy for secondary prevention in patients with a history of atherosclerotic cardiovascular disease (ASCVD), but evidence is wanting in the case of primary prevention, low-risk individuals, and elderly adults 65+. Statins are effective in lowering low-density lipoprotein (LDL), which has long been a target for treatment decisions. We discuss the weakening dependence between cholesterol levels and mortality as a function of age and highlight recent findings on lipoprotein subfractions and other superior markers of ASCVD risk. The efficacy of statins is compared for distinct subsets of patients based on age, diabetes, ASCVD, and coronary artery calcium (CAC) status. Most cardiovascular risk calculators heavily weight age and overestimate one's absolute risk of ASCVD, particularly in very old adults. Improvements in risk assessment enable the identification of specific patient populations that benefit most from statin treatment. Derisking is particularly important for adults over 75, in whom treatment benefits are reduced and adverse musculoskeletal effects are amplified. The CAC score stratifies the benefit effect size obtainable with statins, and forms of coenzyme Q are discussed for improving patient outcomes. Robust risk estimator tools and personalized, evidence-based approaches are needed to optimally reduce cardiovascular events and mortality rates through administration of cholesterol-lowering medications.

MeSH Terms

-

Keywords

cardiovascular disease; cardiovascular risk calculators; coenzyme Q; coronary artery calcification; geriatrics; lipoprotein subfractions; low-density lipoprotein cholesterol; primary prevention; risk biomarkers; statins

The hypothalamic-pituitary-gonadal axis controls muscle stem cell senescence through autophagosome clearance.

Abstract

With organismal aging, the hypothalamic-pituitary-gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown. We generated muscle stem cell (MuSC)-specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short-term and long-term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30-month-old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed. Disrupting the HPG axis results in impaired muscle regeneration [wild-type (WT) vs. dKO, P < 0.0001; Veh vs. Antide, P = 0.004]. The expression of DNA damage marker (in WT = 7.0 ± 1.6%, dKO = 32.5 ± 2.6%, P < 0.01; in Veh = 13.4 ± 4.5%, Antide = 29.7 ± 5.5%, P = 0.028) and senescence-associated β-galactosidase activity (in WT = 3.8 ± 1.2%, dKO = 10.3 ± 1.6%, P < 0.01; in Veh = 2.1 ± 0.4%, Antide = 9.6 ± 0.8%, P = 0.005), as well as the expression levels of senescence-associated genes, p16 and p21 , was significantly increased in the MuSCs, indicating that genetic and pharmacological inhibition of the HPG axis recapitulates the progressive aging process of MuSCs. Mechanistically, the ablation of sex hormone signalling reduced the expression of transcription factor EB (Tfeb) and Tfeb target gene in MuSCs, suggesting that sex hormones directly induce the expression of Tfeb, a master regulator of the autophagy-lysosome pathway, and consequently autophagosome clearance. Transduction of the Tfeb in naturally aged MuSCs increased muscle mass [control geriatric MuSC transplanted tibialis anterior (TA) muscle = 34.3 ± 2.9 mg, Tfeb-transducing geriatric MuSC transplanted TA muscle = 44.7 ± 6.7 mg, P = 0.015] and regenerating myofibre size [eMyHC tdTomato myofibre cross-section area (CSA) in control vs. Tfeb, P = 0.002] after muscle injury. Our data show that the HPG axis systemically controls autophagosome clearance in MuSCs through Tfeb and prevents MuSCs from senescence, suggesting that sustained HPG activity throughout life regulates autophagosome clearance to maintain the quiescence of MuSCs by preventing senescence until advanced age.

MeSH Terms

-

Keywords

Aging; Autophagy; Cellular senescence; Muscle regeneration; Muscle stem cell; Sex steroid hormones

Probing menstrual bloodstain aging with fluorescence spectroscopy.

Abstract

Menstrual blood (MB) is a common and important type of forensic evidence, especially in sexual assault cases. MB is composed of peripheral blood (PB), vaginal fluid, and endometrial cells of the uterine wall. In forensic investigations, the differentiation of MB and PB can determine whether the blood present is a result of tissue damage from an assault or a natural cause and thus help to reconstruct the event. Understanding how menstrual blood changes is necessary to develop a method for bloodstain aging. Fluorescence spectroscopy, a promising spectroscopic method for bloodstain analysis, was used to probe the biochemical changes that occur over time in menstrual bloodstains. It was found that steady-state fluorescence spectra underwent significant changes over first nine hours post deposition. The underlying mechanism of fluorescence changes was proposed to involve the kinetic transformation of three fluorophores: tryptophan, nicotinamide adenine dinucleotide and flavins.

MeSH Terms

-

Keywords

Aging; Analytical methods; Blood; Fluorescence spectroscopy; Forensics

Winter honeybee ([i]Apis mellifera[/i]) populations show greater potential to induce immune response than summer ones after immune stimuli.

Abstract

In the temperate climates of middle Europe and North America, two distinct honeybee ([i]Apis mellifera[/i]) populations are found in colonies: short-living summer bees emerge in spring and survive until summer, whereas long-living winter bees emerge in late August and overwinter. Besides the difference in their life spans, each of these populations fulfills a different role in the colonies and individual bees have distinct physiological and immunological adaptations depending on their roles. For instance, winter worker bees have higher vitellogenin levels and larger reserves of nutrients in the fat body than summer bees. The differences between the immune systems of both populations are well described at the constitutive level; however, our knowledge of its inducibility is still very limited. In this study, we focus on the response of 10-day-old honeybee workers to immune challenges triggered [i]in vivo[/i] by injecting heat-killed bacteria, with particular focus on honeybees that emerge and live under hive conditions. Responses to bacterial injections differed between summer and winter bees. The latter induced more intense response, including higher expression of antimicrobial genes and antimicrobial activity, as well as a significant decrease in vitellogenin gene expression and its concentration in the hemolymph. The intense immune response observed in winter honeybees may contribute to our understanding of the relationships between colony fitness and infection with pathogens, as well as its association with successful overwintering.

MeSH Terms

-

Keywords

Antimicrobial peptides; Honeybee; Humoral immunity; Immune system; Longevity

Home-based exercise can be beneficial for counteracting sedentary behavior and physical inactivity during the COVID-19 pandemic in older adults.

Abstract

The novel pandemic called coronavirus disease 2019 (COVID-19), as a global public health emergency, seems to be having a major impact on physical activity (PA) behaviors. Older adults are at high risk of death from the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Health authorities around the world have been implementing preventive health measures, including quarantine and self-isolation, to mitigate the COVID-19 outbreak. This period is characterized by cessation of outdoor exercising. During this period of lockdown, PA has been one of the rare reasons for going out in some countries. To avoid the harmful effects of periods of exercise cessation, PA could be prescribed to older adults, which is of great importance for breaking their sedentary lifestyle and improving their immunity. The present review discusses the potential impacts of COVID-19 pandemic on sedentary behavior and physical inactivity in older adults. The importance of performing PA to reduce the harmful effects of COVID-19 pandemic is discussed, and useful recommendations on home-based exercise for the older adults to maintain their level of independence, physical and mental health as well as their wellbeing are provided.

MeSH Terms

-

Keywords

Coronavirus; aging; exercise; health; physical activity; sedentary

Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

Abstract

In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu-) educational attainment subgroups, were available in an Italian-Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu- subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu- subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray-white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.

MeSH Terms

-

Keywords

aging; education attainment; exact low-resolution brain electromagnetic source tomography (eLORETA); mild cognitive impairment due to Alzheimer’s disease (ADMCI); resting state electroencephalographic (rsEEG) rhythms

Reduced RING finger protein 10 expression in macrophages is associated with aging-related inflammation.

Abstract

Age-associated decline of the immune system is referred to as immunosenescence. The E3 ligase RING finger 10 (RNF10) has long been associated with the innate immune response, but a potential role in immunosenescence has not previously been reported. In the present study, we identified that RNF10 expression is lower in aged mouse macrophages than in young cells. After lipopolysaccharide (LPS) stimulation, RNF10 expression remained at a basal low level in aged mouse cells, but declined sharply in young mouse cells. Knockdown of RNF10 enhanced both the nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) signaling pathways and thus enhanced proinflammatory cytokines and type I interferons (IFN-I) in macrophages, promoting clearance of L. monocytigenes. These findings indicate that dysregulated expression of RNF10 is associated with age-associated immune dysfunction, and RNF10 may thus be a potential target for the treatment of age-related inflammatory diseases.

MeSH Terms

-

Keywords

E3 ubiquitin ligase; RNF10; immunosenescence; inflammation; macrophages

Loss of Atg7 causes chaotic nucleosome assembly of mouse bone marrow CD11b Ly6G myeloid cells.

Abstract

Atg7, a critical component of autophagy machinery, is essential for counteracting hematopoietic aging. However, the non-autophagic role of Atg7 on hematopoietic cells remains fundamentally unclear. In this study, we found that loss of Atg7, but not Atg5, another autophagy-essential gene, in the hematopoietic system reduces CD11b myeloid cellularity including CD11b Ly6G and CD11b Ly6G populations in mouse bone marrow. Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11b Ly6G , but not the CD11b Ly6G compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11b Ly6G population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11b Ly6G population.

MeSH Terms

-

Keywords

Atg7; aging; histone H3.1; nucleosome assembly

Silencing of FOREVER YOUNG FLOWER Like Genes from Phalaenopsis Orchids Promotes Flower Senescence and Abscission.

Abstract

Ectopic expression of FOREVER YOUNG FLOWER (FYF) delays floral senescence and abscission in transgenic Arabidopsis. To analyze the FYF function in Phalaenopsis orchids, two FYF-like genes (PaFYF1/2) were identified. PaFYF1/2 were highly expressed in young Phalaenopsis flowers, and their expression decreased significantly afterward until flower senescence. This pattern was strongly correlated with the process of flower senescence and revealed that PaFYF1/2 function to suppress senescence/abscission during early flower development. Interestingly, in flowers, PaFYF1 was consistently expressed less in petals than in lips/sepals, whereas PaFYF2 was expressed relatively evenly in all flower organs. This difference suggests a regulatory modification of the functions of PaFYF1 and PaFYF2 during Phalaenopsis flower evolution. Delayed flower senescence and abscission, which were unaffected by ethylene treatment, were observed in 35S::PaFYF1/2 and 35S::PaFYF1/2+SRDX transgenic Arabidopsis plants due to downregulation of the ethylene signaling and abscission-associated genes EDF1-4, IDA and BOP1/2. These results suggest a possible repressor role for Phalaenopsis PaFYF1/2 in controlling floral senescence/abscission by suppressing ethylene signaling and abscission-associated genes. To further validate the function of PaFYF1/2, PaFYF1/2-VIGS (virus-induced gene silencing) Phalaenopsis were generated and analyzed. Promotion of senescence and abscission was observed in PaFYF1/2-VIGS Phalaenopsis flowers by the upregulation of PeEDF1/2, PeSAG39 and PeBOP1/2 expression, early occurrence of greening according to their increased chlorophyll content and reduction of water content in flower organs. Our results support that PaFYF1/2 function as transcriptional repressors to prohibit flower senescence and abscission in Phalaenopsis.

MeSH Terms

-

Keywords

         FOREVER YOUNG FLOWER
       ; 
         Phalaenopsis orchids; Abscission; Ethylene responses; MADS-box gene; Senescence

Omega-3 supplementation improves isometric strength but not muscle anabolic and catabolic signaling in response to resistance exercise in healthy older adults.

Abstract

Old skeletal muscle exhibits decreased anabolic sensitivity, eventually contributing to muscle wasting. Besides anabolism, also muscle inflammation and catabolism are critical players in regulating the old skeletal muscle's sensitivity. Omega-3 fatty acids (ω-3) are an interesting candidate to reverse anabolic insensitivity via anabolic actions. Yet, it remains unknown whether ω-3 also attenuates muscle inflammation and catabolism. The present study investigates the effect of ω-3 supplementation on muscle inflammation and metabolism (anabolism/catabolism) upon resistance exercise (RE). Twenty-three older adults (OA) (65-84yr;8♀) were randomized to receive ω-3 (~3g·d -1) or corn oil (PLAC) and engaged in a 12-wk RE program (3x·wk -1). Before and after intervention, muscle volume, strength and systemic inflammation were assessed, and muscle biopsies were analysed for markers of anabolism, catabolism and inflammation. Isometric knee-extensor strength increased in ω-3 (+12.2%), but not in PLAC (-1.4%; pinteraction=0.015), whereas leg press strength improved in both conditions (+27.1%; ptime<0.001). RE, but not ω-3, decreased inflammatory (p65NF-κB) and catabolic (FOXO1, LC3b) markers, and improved muscle quality. Yet, muscle volume remained unaffected by RE and ω-3. Accordingly, muscle anabolism (mTORC1) and plasma CRP remained unchanged by RE and ω-3, whereas serum IL-6 tended to decrease in ω-3 (pinteraction=0.07). These results show that, despite no changes in muscle volume, RE-induced gains in isometric strength can be further enhanced by ω-3. However, ω-3 did not improve RE-induced beneficial catabolic or inflammatory adaptations. Irrespective of muscle volume, gains in strength (primary criterion for sarcopenia) might be explained by changes in muscle quality due to muscle inflammatory or catabolic signaling.

MeSH Terms

-

Keywords

Muscle wasting; aging; anabolic resistance; inflammation; resistance training; sarcopenia

Anti-aging technoscience & the biologization of cumulative inequality: Affinities in the biopolitics of successful aging.

Abstract

This paper charts the emergence of under-remarked affinities between contemporary anti-aging technoscience and some social scientific work on biological aging. Both have recently sought to develop increasingly sophisticated operationalizations of age, aging and agedness as biological phenomena, in response to traditional notions of normal and chronological aging. Rather than being an interesting coincidence, these affinities indicate the influence of a biopolitics of successful aging on government, industry and social science. This biopolitics construes aging as a personal project that is mastered through specific forms of entrepreneurial individual action, especially consumption practices. Social scientists must remain alert to this biopolitics and its influence on their own work, because the individualization of cumulative inequalities provides intellectual and moral justifications for anti-aging interventions that exploit those inequalities.

MeSH Terms

-

Keywords

Active aging; Biological age; Biomarker; Cumulative advantage; Functional age

Associations between Alzheimer's disease polygenic risk scores and hippocampal subfield volumes in 17,161 UK Biobank participants.

Abstract

Hippocampal volume is an important biomarker of Alzheimer's disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRS ) have been inadequately investigated. We examined these associations in 17,161 cognitively normal UK Biobank participants (44-80 years). Age was negatively associated with all the hippocampal subfield volumes and females had smaller volumes than men. Higher PRS was associated with lower volumes in the bilateral whole hippocampus, hippocampal-amygdala-transition-area, and hippocampal tail; right subiculum; left cornu ammonis 1, cornu ammonis 4, molecular layer, and granule cell layer of dentate gyrus. Older individuals (median age 63 years, n = 8984) showed greater subfield vulnerability to high PRS compared to the younger group (n = 8177), but the effect did not differ by sex. The pattern of subfield involvement in relation to the PRS in community dwelling healthy individuals sheds additional light on the pathogenesis of AD.

MeSH Terms

-

Keywords

Aging; Alzheimer’s disease; Hippocampal subfields; Polygenic risk score

Maybe Age Isn't Just a Number: Elderly-onset IBD Is a Demographic Deserving of Specific Considerations.

Abstract

---

MeSH Terms

-

Keywords

Crohn’s disease; aging; biologics; colitis; infections

Effect of air-abrasion at pre- and/or post-sintered stage and hydrothermal aging on surface roughness, phase transformation, and flexural strength of multilayered monolithic zirconia.

Abstract

This study aimed to evaluate the effect of air-abrasion/sintering order and autoclave aging on the surface roughness (Ra), phase transformation, and biaxial flexural strength (BFS) of monolithic zirconia. A total of 104 monolithic zirconia specimens (Katana ML) were divided into eight groups according to airborne-particle abrasion protocols and hydrothermal aging: control (non-aged: C-, aged: C+), air-abrasion before sintering (BS-, BS+), air-abrasion after sintering (AS-, AS+), and air-abrasion before and after sintering (BAS-, BAS+). A steam autoclave was used for accelerated aging, and Ra values were measured with a surface profilometer. All specimens were analyzed by X-ray diffraction to determine any phase transformation on the zirconia surface. BFS was measured by using the piston-on-three-balls method. Scanning electron microscopy and atomic force microscopy were performed on one specimen per group. BS and BAS groups showed higher Ra values compared with groups C and AS. The aging process significantly increased the monoclinic phase content of all specimens. Lower monoclinic levels were found in AS+ and BAS+ compared with other aged groups. The AS groups exhibited higher flexural strength values relative to control groups, whereas BS groups exhibited significantly lower flexural strength values (p < .05). There was no reduction in flexural strength by using the BAS protocol. Air-abrasion of zirconia at the pre-sintered stage only is not recommended in clinical use because of the remarkable decrease in flexural strength.

MeSH Terms

-

Keywords

airborne-particle abrasion; flexural strength; hydrothermal aging; monolithic zirconia; phase transformation

Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan.

Abstract

Caloric restriction (CR), the reduction of caloric intake without inducing malnutrition, is the most reproducible method of extending health and lifespan across numerous organisms, including humans. However, with nearly one-third of the world's population overweight, it is obvious that caloric restriction approaches are difficult for individuals to achieve. Therefore, identifying compounds that mimic CR is desirable to promote longer, healthier lifespans without the rigors of restricting diet. Many compounds, such as rapamycin (and its derivatives), metformin, or other naturally occurring products in our diets (nutraceuticals), induce CR-like states in laboratory models. An alternative to CR is the removal of specific elements (such as individual amino acids) from the diet. Despite our increasing knowledge of the multitude of CR approaches and CR mimetics, the extent to which these strategies overlap mechanistically remains unclear. Here we provide an update of CR and CR mimetic research, summarizing mechanisms by which these strategies influence genome function required to treat age-related pathologies and identify the molecular fountain of youth.

MeSH Terms

-

Keywords

amino acid restriction; caloric restriction; caloric restriction mimetics; general control nonderepressible 2 (GCN2); healthspan; lifespan; mammalian target of rapamycin (mTOR)

Heart and neural crest derivative 2-induced preservation of sympathetic neurons attenuates sarcopenia with aging.

Abstract

Sarcopenia, or age-dependent decline in muscle force and power, impairs mobility, increasing the risk of falls, institutionalization, co-morbidity, and premature death. The discovery of adrenoceptors, which mediate the effects of the sympathetic nervous system (SNS) neurotransmitter norepinephrine on specific tissues, sparked the development of sympathomimetics that have profound influence on skeletal muscle mass. However, chronic administration has serious side effects that preclude their use for muscle-wasting conditions. Interventions that can adjust neurotransmitter release to changing physiological demands depend on understanding how the SNS affects neuromuscular transmission, muscle motor innervation, and muscle mass. We examined age-dependent expression of the heart and neural crest derivative 2 (Hand2), a critical transcription factor for SN maintenance, and we tested the possibility that inducing its expression exclusively in sympathetic neurons (SN) will prevent (i) motor denervation, (ii) impaired neuromuscular junction (NMJ) transmission, and (iii) loss of muscle mass and function in old mice. To test this hypothesis, we delivered a viral vector carrying Hand2 expression or an empty vector exclusively in SNs by vein injection in 16-month-old C57BL/6 mice that were sacrificed 6 months later. Techniques include RNA-sequencing, real-time PCR, genomic DNA methylation, viral vector construct, tissue immunohistochemistry, immunoblot, confocal microscopy, electrophysiology, and in vivo mouse physical performance. Hand2 expression declines throughout life, but inducing its expression increased (i) the number and size of SNs, (ii) muscle sympathetic innervation, (iii) muscle weight and force and whole-body strength, (iv) myofiber size but not muscle fibre-type composition, (v) NMJ transmission and nerve-evoked muscle force, and (vi) motor innervation in old mice. Additionally, the SN controls a set of genes to reduce inflammation and to promote transcription factor activity, cell signalling, and synapse in the skeletal muscle. Hand2 DNA methylation may contribute, at least partially, to gene silencing. Selective expression of Hand2 in the mouse SNs from middle age through old age increases muscle mass and force by (i) regulating skeletal muscle sympathetic and motor innervation; (ii) improving acetylcholine receptor stability and NMJ transmission; (iii) preventing inflammation and myofibrillar protein degradation; (iv) increasing autophagy; and (v) probably enhancing protein synthesis.

MeSH Terms

-

Keywords

Aging; Denervation; Neuromuscular junction; Sarcopenia; Skeletal muscle; Sympathetic nervous system

Contributions of Hippocampal Volume to Cognition in Healthy Older Adults.

Abstract

The association between hippocampal volume and memory is continuing to be characterized in healthy older adults. Prior research suggests smaller hippocampal volume in healthy older adults is associated with poorer episodic memory and processing speed, as well as working memory, verbal learning, and executive functioning as measured by the NIH Toolbox Fluid (Fluid Cognition Composite, FCC) and Crystalized Cognition Composites (CCC). This study aimed to replicate these findings and to evaluate the association between: (1) hippocampal asymmetry index and cognition; and (2) independent contributions of the left and right hippocampal volume and cognition in a large sample of healthy older adults.  : One-hundred and eighty-three healthy older adults (M age = 71.72, SD = 5.3) received a T1-weighted sequence on a 3T scanner. Hippocampal subfields were extracted using FreeSurfer 6.0 and combined to provide left, right, and total hippocampal volumes. FCC subtests include Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, List Sorting, Picture Sequence Memory, and Pattern Comparison. CCC subtests include Picture Vocabulary and Oral Reading Recognition. Multiple linear regressions were performed predicting cognition composites from the total, left and right, and asymmetry of hippocampal volume, controlling for sex, education, scanner, and total intracranial volume. Multiple comparisons in primary analyses were corrected using a false discovery rate (FDR) of [i]p[/i] < 0.05.  : FCC scores were positively associated with total ([i]β[/i] = 0.226, FDR [i]q[/i] = 0.044) and left ([i]β[/i] = 0.257, FDR [i]q[/i] = 0.024) hippocampal volume. Within FCC, Picture Sequence Memory scores positively associated with total ([i]β[/i] = 0.284, [i]p[/i] = 0.001) and left ([i]β[/i] = 0.98, [i]p[/i] = 0.001) hippocampal volume. List Sorting scores were also positively associated with left hippocampal volume ([i]β[/i] = 0.189, [i]p[/i] = 0.029).  : These results confirm previous research suggesting that bilateral hippocampal volume is associated with FCC, namely episodic memory. The present study also suggests the left hippocampal volume may be more broadly associated with both episodic and working memory. Studies should continue to investigate lateralized hippocampal contributions to aging processes to better identify predictors of cognitive decline.

MeSH Terms

-

Keywords

NIH toolbox; aging; brain volume; cognition; hippocampus; magnetic resonance imaging

Addressing stereotypes of aging and interest in careers working with older adults through education.

Abstract

Negative stereotypes about older adults are increasing and contributing to a shortage of professionals in gerontology. Building on the PEACE model (Positive Education about Aging and Contact Experiences), two experiments used education to address stereotypes associated with older adults. Participants were randomly assigned to read brief articles that: challenged stereotypes about older adults (condition 1), challenged stereotypes about careers working with older adults (condition 2), challenged both stereotypes (condition 3), or described careers in general (control; condition 4). In Study 1, 399 undergraduates in all 3 experimental conditions (vs. control participants) reported lower levels of ageism, more positive age perceptions, and more aging knowledge in an immediate and delayed (1-2 weeks) post-test. In Study 2, 446 national community participants (ages 18- 25) in all experimental conditions (vs. control participants) reported greater positive age perceptions, aging knowledge, and interest in psychology and social work careers with older adults in an immediate post-test. These findings highlight the promise of using brief online methods to challenge stereotypes, provide more positive and accurate views of aging and older adults, and increase interest in careers working with older adults. Implications are discussed.

MeSH Terms

-

Keywords

Experiment; geriatrics; geropsychology; intervention; prejudice reduction

Mutation in histone deacetylase HDA-3 leads to shortened locomotor healthspan in [i]Caenorhabditis elegans[/i].

Abstract

Some genes are essential for survival, while other genes play modulatory roles on health and survival. Genes that play modulatory roles may promote an organism's survival and health by fine-tuning physiological processes. An unbiased search for genes that alter an organism's ability to maintain aspects of health may uncover modulators of lifespan and healthspan. From an unbiased screen for [i]Caenorhabditis elegans[/i] mutants that show a progressive decline in motility, we aimed to identify genes that play a modulatory role in maintenance of locomotor healthspan. Here we report the involvement of [i]hda-3,[/i] encoding a class I histone deacetylase, as a genetic factor that contributes in the maintenance of general health and locomotion in [i]C. elegans[/i]. We identified a missense mutation in HDA-3 as the causative mutation in one of the isolated strains that show a progressive decline in maximum velocity and travel distance. From transcriptome analysis, we found a cluster of genes on Chromosome II carrying BATH domains that were downregulated by [i]hda-3[/i]. Furthermore, downregulation of individual [i]bath[/i] genes leads to significant decline in motility. Our study identifies genetic factors that modulate the maintenance of locomotor healthspan and may reveal potential targets for delaying age-related locomotor decline.

MeSH Terms

-

Keywords

BATH domain; age-related locomotor impairment; aging; hda-3; longevity

CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta.

Abstract

An adequate development of the placenta includes trophoblast differentiation with the processes of trophoblast migration, invasion, cellular senescence and apoptosis which are all crucial to establishing a successful pregnancy. Altered placental development and function lead to placental diseases such as preeclampsia (PE) which is mainly characterized by insufficient trophoblast invasion and abnormally invasive placenta (AIP) disorders ([i]Placenta accreta[/i], [i]increta[/i], or [i]percreta)[/i] which are characterized by excessive trophoblast invasion. Both of them will cause maternal and fetal morbidity/mortality. However, the etiology of these diseases is still unclear. Our previous study has shown that the matricellular protein [i]nephroblastoma overexpressed[/i] (NOV, CCN3) induces G0/G1 cell cycle arrest, drives trophoblast cells into senescence and activates FAK and Akt kinases resulting in reduced cell proliferation and enhanced migration capability of the human trophoblast cell line SGHPL-5. The present study focuses on whether CCN3 can alter cell cycle-regulated pathways associated with trophoblast senescence and invasion activity in pathological versus gestational age-matched control placentas. Cell cycle regulator proteins were investigated by immunoblotting and qPCR. For localization of CCN3, p16, p21, and Cyclin D1 proteins, co-immunohistochemistry was performed. In early-onset PE placentas, CCN3 was expressed at a significantly lower level compared to gestational age-matched controls. The decrease of CCN3 level is associated with an increase in p53, Cyclin E1 and pRb protein expression, whereas the level of cleaved Notch-1, p21, Cyclin D1, pFAK, pAKT, and pmTOR protein decreased. In term AIP placentas, the expression of CCN3 was significantly increased compared to matched term controls. This increase was correlated to an increase in p53, p16, p21, Cyclin D1, cleaved Notch-1, pFAK, pAkt, and pmTOR whereas pRb was significantly decreased. However, in late PE and early AIP placentas, no significant differences in CCN3, p16, p21, Cyclin D1, p53, and cleaved Notch-1 expression were found when matched to appropriate controls. CCN3 expression levels are correlated to markers of cell cycle arrest oppositely in PE and AIP by activating the FAK/AKT pathway in AIP or down-regulating in PE. This may be one mechanism to explain the different pathological features of placental diseases, PE and AIP.

MeSH Terms

-

Keywords

CCN3; abnormally invasive placenta; invasion; preeclampsia; senescence; trophoblast

Understanding the Clinical Features of Coronavirus Disease 2019 From the Perspective of Aging: A Systematic Review and Meta-Analysis.

Abstract

An outbreak of novel coronavirus (2019-nCov) infection is now widespread in multiple countries. Compared with adult patients, elderly patients have not received enough attention. The aim of the meta-analysis was to assess the clinical characteristics of elder patients with COVID-19. A deep literature search was performed in the databases through August 21, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using analysis models. Three studies including 2046 infected patients were precisely evaluated, and the results show that the elderly group has a higher risk of hypertension, diabetes, and cardiovascular disease than the younger patients. Their total white blood cells are higher than that of the younger patients, and their lymphocytes are relatively reduced compared with the younger patients. We comprehensively assessed the clinical characteristics of patients of different ages with COVID-19 and found that elder patients had a high risk of chronic cardiovascular and metabolism comorbidities. The characteristic clinical manifestations and laboratory examinations of elderly patients support their excessive inflammation and weak immune defenses against 2019-nCoV. All these findings provide important information for understanding the general clinical characterization of the aging immune defense against the virus and enhancing the public awareness of the prevention and treatment of elder patients in the COVID-19 pandemic.

MeSH Terms

-

Keywords

2019 coronavirus disease; 2019 novel coronavirus; aging patients; clinical characteristics; immune senescence; meta-analysis

A systematic review of center of pressure measures to quantify gait changes in older adults.

Abstract

Measures of gait center of pressure (COP) can be recorded using simple available technologies in clinical settings and thus can be used to characterize gait quality in older adults and its relationship to falls. The aim of this systematic review was to investigate the association between measures of gait COP and aging and falls. A comprehensive search of electronic databases including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL (EBSCO), Ageline (EBSCO) and Scopus was performed. The initial search yielded 2809 papers. After removing duplicates and applying study inclusion/exclusion criteria, 34 papers were included in the review. Gait COP has been examined during three tasks: normal walking, gait initiation, and obstacle negotiation. The majority of studies examined mean COP position and velocity as outcome measures. Overall, gait in older adults was characterized by more medial COP trajectory in normal walking and lower average anterior-posterior and medio-lateral COP displacements and velocity in both gait initiation and obstacle crossing. Moreover, findings suggest that Tai chi training can enhance older adults' balance control during gait initiation as demonstrated by greater COP backward, medial and forward shift in all three phases of gait initiation. These findings should be interpreted cautiously due to inadequacy of evidence as well as methodological limitations of the studies such as small sample size, limited numbers of 'fallers', lack of a control group, and lack of interpretation of COP outcomes with respect to fall risk. COP measures can be adopted to assess fall-related gait changes in older adults but more complex measures of COP that reveal the dynamic nature of COP behavior in step-to-step variations are needed to adequately characterize gait changes in older adults.

MeSH Terms

-

Keywords

Biomechanics; Geriatrics; Stability; Walking

Engaging patients as partners in a multicentre trial of spinal versus general anaesthesia for older adults.

Abstract

Engaging patients-defined broadly as individuals with lived experience of a given condition, family members, caregivers, and the organisations that represent them-as partners in research is a priority for policymakers, funders, and the public. Nonetheless, formal efforts to engage patients are absent from most studies, and models to support meaningful patient engagement in clinical anaesthesia research have not been previously described. Here, we review our experience in developing and implementing a multifaceted patient engagement strategy within the Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN) surgery trial, an ongoing randomised trial comparing spinal vs general anaesthesia for hip fracture surgery in 1600 older adults across 45 hospitals in the USA and Canada. This strategy engaged patients and their representatives at both the level of overall trial oversight and at the level of individual recruiting sites. Activities spanned a continuum ranging from events designed to elicit patients' input on key decisions to longitudinal collaborations that empowered patients to actively participate in decision-making related to trial design and management. Engagement activities were highly acceptable to participants and led to concrete changes in the design and conduct of the REGAIN trial. The REGAIN experience offers a model for future efforts to engage patients as partners in clinical anaesthesia research, and highlights potential opportunities for investigators to increase the relevance of anaesthesia studies by incorporating patient voices and perspectives into the research process.

MeSH Terms

-

Keywords

anaesthesia; geriatrics; hip fracture; patient advocacy; patient engagement; research methods; shared decision-making

Rejuvenation of Senescent Endothelial Progenitor Cells by Extracellular Vesicles Derived From Mesenchymal Stromal Cells.

Abstract

Mesenchymal stromal cell (MSC) transplantation is a form of the stem-cell therapy that has shown beneficial effects for many diseases. The use of stem-cell therapy, including MSC transplantation, however, has limitations such as the tumorigenic potential of stem cells and the lack of efficacy of aged autologous cells. An ideal therapeutic approach would keep the beneficial effects of MSC transplantation while circumventing the limitations associated with the use of intact stem cells. This study provides proof-of-concept evidence that MSC-derived extracellular vesicles represent a promising platform to develop an acellular therapeutic approach that would just do that. Extracellular vesicles are membranous vesicles secreted by MSCs and contain bioactive molecules to mediate communication between different cells. Extracellular vesicles can be taken up by recipient cells, and once inside the recipient cells, the bioactive molecules are released to exert the beneficial effects on the recipient cells. This study, for the first time to our knowledge, shows that extracellular vesicles secreted by MSCs recapitulate the beneficial effects of MSCs on vascular repair and promote blood vessel regeneration after ischemic events. Furthermore, MSCs from aged donors can be engineered to produce extracellular vesicles with improved regenerative potential, comparable to MSCs from young donors, thus eliminating the need for allogenic young donors for elderly patients.

MeSH Terms

-

Keywords

BM, bone marrow; CVD, cardiovascular disease; EC, endothelial cell; EPC, endothelial progenitor cell; EV, extracellular vesicle; FBS, fetal bovine serum; MEM, minimum essential medium; MI, myocardial infarction; MSC, mesenchymal stromal cell; NTA, nanotracking analysis; PBS, phosphate-buffered saline; TEV, tailored extracellular vesicle; VEGF, vascular endothelial growth factor; acellular; angiogenesis; extracellular vesicles; lin− BMC, lineage negative bone marrow cell; miR, microRNA; qPCR, quantitative transcription polymerase chain reaction; regeneration; senescence

Inflammaging in Endemic Areas for Infectious Diseases.

Abstract

Immunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory [i]versus[/i] remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts.

MeSH Terms

-

Keywords

aging; chronic infection; dietary components; genetics; inflammaging; inflammation; microbiota

[Key Molecular Mechanisms of Aging, Biomarkers, and Potential Interventions].

Abstract

The mechanisms of aging are described at the molecular, cell, tissue, and systemic levels. Primary age-dependent molecular lesions activate the cell stress response to compensate for the resulting defects, but the mechanisms that recover and maintain homeostasis are gradually deteriorated. When the amount of errors reaches a critical threshold in regulatory networks, a phase transition from health to disease occurs at the systemic level. The review considers the approaches to quantitative assessment of the aging process (biomarkers of aging) and promising interventions to slow down the aging process and to reduce the risk of age-dependent diseases.

MeSH Terms

-

Keywords

age-dependent diseases; aging; biomarkers of aging; geroprotectors

Effects of Age on Inflammatory Profiles and Nutrition/Energy Metabolism in Domestic Cats.

Abstract

Animals tend to increase in body weight and body condition score (BCS) with aging. Serum diagnostic markers related to energy metabolism may show changes even in healthy cats with aging. Seventy domestic cats were recruited for this study. Based upon the modified AAFP-AAHA Feline Life Stage Guidelines, animals were divided into six groups: Junior (7 months-2 years), Prime (3 -6 years), Mature (7-10 years), Senior (11-14 years), Geriatric-obese (15 years ≤) and Geriatric-thin (15 years ≤). Their body condition scores (BCS) ranged from 3/9 to 9/9. Changes in metabolites, inflammatory markers, hormone concentrations and enzyme activities related to energy metabolism were investigated in serum of 70 domestic cats of various ages. Serum glucose (GLU) concentrations in the Mature, Senior, and Geriatric-obese groups were significantly higher than those in the Junior group. Serum amyloid A (SAA) concentrations in the Geriatric-thin group were significantly increased compared with the Junior group. SAA concentrations in the Geriatric-obese group tended to increase although there were no statistically significant differences. In the Mature, Senior, Geriatric-obese and Geriatric-thin groups, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, an energy metabolic indicator, tended to decrease compared with the Junior group. In the Senior group, triglyceride (TG) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese and Geriatric-thin groups, blood urea nitrogen (BUN) concentrations were significantly increased compared with the Junior group. In the Geriatric-obese group, albumin (ALB) concentrations were decreased compared with the Junior group. Aged domestic cats tend to increase in body weight and BCS. In addition, serum GLU, TG, SAA, and BUN concentrations increased and serum ALB concentrations and M/L ratio decreased. These diagnostic markers may be useful to detect small changes related to energy metabolism with aging that may cause obesity with light inflammation in healthy cats.

MeSH Terms

-

Keywords

M/L ratio; SAA; aging; domestic cats; obesity

Prevalence and prognostic value of the coexistence of anaemia and frailty in older patients with heart failure.

Abstract

There have been no investigations of the prevalence and clinical implications of coexistence of anaemia and frailty in older patients hospitalized with heart failure (HF) despite their association with adverse health outcomes. The present study was performed to determine the prevalence and prognostic value of the coexistence of anaemia and frailty in hospitalized older patients with HF. We performed post hoc analysis of consecutive hospitalized HF patients ≥65 years old enrolled in the FRAGILE-HF, which was the prospective, multicentre, observational study. Anaemia was defined as haemoglobin < 13 g/dL in men and <12 g/dL in women, and frailty was evaluated according to the Fried phenotype model. The study endpoint was all-cause mortality. Of the total of 1332 patients, 1217 (median age, 81 years; 57.4% male) were included in the present study. The rates of anaemia and frailty in the study population were 65.7% and 57.0%, respectively. The patients were classified into the non-anaemia/non-frail group (16.6%), anaemia/non-frail group (26.4%), non-anaemia/frail group (17.7%), and anaemia/frail group (39.3%). A total of 144 patients died during 1 year of follow-up. In multivariate analyses, only the anaemia/frail group showed a significant association with elevated mortality rate (adjusted hazard ratio, 1.94; 95% confidence interval, 1.02-3.70; P = 0.043), compared with the non-anaemia/non-frail group after adjusting for other covariates. Coexistence of anaemia and frailty are prevalent in hospitalized older patients with HF, and it has a negative impact on mortality.

MeSH Terms

-

Keywords

Anaemia; Frailty; Geriatrics; Heart failure in elderly; Prognosis

[Age-related features of the relationship between the content of vascular endothelial growth factor and indicators of lipid metabolism and extracellular matrix metabolism in men in the European part of the Russian Arctic.]

Abstract

The content of vascular endothelial growth factor-A (VEGF-A) in blood plasma and its relationship with lipid and extracellular matrix metabolism in working-aged men (19-69 years), living and working in the European part of the Arctic zone of the Russian Federation (Russian Arctic), were studied. No age dependence of the plasma VEGF-A content was found. The correlation analysis, performed in different age groups, revealed significant associations of VEGF-A level with lipid parameters (CS, LDL-C, Apo B, atherogenicity coefficient, Apo B /Apo A1 ratio) and extracellular matrix metabolism (blood TIMP-4, MMP-2, MMP-3, MMP-9, hyaluronan, total and peptide-bound hydroxyproline, glycosaminoglycans). The established correlations indicate the formation of relationships between angiogenesis, atherogenesis and fibrosis at a specific period of life of northerners in the Russian Arctic.

MeSH Terms

-

Keywords

European part of the Arctic zone of the Russian Federation; aging; angiogenesis; hypoxia; vascular endothelial growth factor (VEGF)

Relationship between the disrupted topological efficiency of the structural brain connectome and glucose hypometabolism in normal aging.

Abstract

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57-84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p < 0.05). In the subregions of the bilateral thalamus, significant correlations between nodal efficiency and cortical metabolism could be observed across subjects. Individual-level analyses indicated that brain regions with higher nodal efficiency tend to exhibit higher metabolic levels, implying a tight coupling between nodal efficiency and glucose metabolism (r = 0.56, p = 1.15 × 10 ). Moreover, efficiency-metabolism coupling coefficient significantly increased with age (r = 0.44, p = 0.0046). Finally, the main findings were also reproducible in the ADNI dataset. Together, our results demonstrate a close coupling between structural brain connectivity and cortical metabolism in normal elderly individuals and provide new insight that improve the present understanding of the metabolic mechanisms of structural brain disconnections in normal aging.

MeSH Terms

-

Keywords

Brain network; Diffusion MRI; FDG-PET; Glucose metabolism; Graph theory; MRI; Normal aging

A Prospective Double-blind, Placebo-controlled Clinical Trial Evaluating the Efficacy of a Novel Combination of Hyaluronic Acid Serum and Antioxidant Cream for Rejuvenation of the Aging Neck.

Abstract

The neck is one of the most common areas affected by the aging process. A novel two product combination system composed of a serum and cream with hyaluronic acid and multiple strong antioxidants were investigated to determine their efficacy and safety in neck rejuvenation.   The objective of this prospective, randomized, double-blind, placebo-controlled clinical trial was to assess the efficacy and safety of a novel serum containing fractionated hyaluronic acid, peptides, and antioxidants for photodamage of the neck.   This was an institutional review board (IRB)-approved, randomized, double blind, placebo-controlled clinical trial involving 31 healthy subjects with moderate-to-severe neck wrinkling corresponding to at least a Grade 2 in wrinkles and score of 4 in elastosis on the Fitzpatrick-Goldman Wrinkle Scale. Twenty subjects were randomized to receive the active cream and serum system, while 11 subjects were randomized to receive the vehicles alone in serum and cream format for a course of two months.   Both active and placebo cream and serum showed improvement of wrinkles, laxity, pigmentation, erythema, dryness, and texture of the skin, and high patient satisfaction scores. Histology of one of the active serums and cream samples revealed improvement in the quality of papillary dermal collagen and increase in the number of elastic fibers in the upper dermis after treatment.   Our prospective, randomized controlled trial showed that the novel serum and cream showed improvement in skin aging on the neck, was well-tolerated by patients, and had a high degree of patient satisfaction.

MeSH Terms

-

Keywords

Aging neck; antioxidant; hyaluronic acid cream; neck rejuvenation

Sex Differences in the Complexity of Healthy Older Adults' Magnetoencephalograms.

Abstract

The analysis of resting-state brain activity recording in magnetoencephalograms (MEGs) with new algorithms of symbolic dynamics analysis could help obtain a deeper insight into the functioning of the brain and identify potential differences between males and females. Permutation Lempel-Ziv complexity (PLZC), a recently introduced non-linear signal processing algorithm based on symbolic dynamics, was used to evaluate the complexity of MEG signals in source space. PLZC was estimated in a broad band of frequencies (2-45 Hz), as well as in narrow bands (i.e., theta (4-8 Hz), alpha (8-12 Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-45 Hz)) in a sample of 98 healthy elderly subjects (49 males, 49 female) aged 65-80 (average age of 72.71 ± 4.22 for males and 72.67 ± 4.21 for females). PLZC was significantly higher for females than males in the high beta band at posterior brain regions including the precuneus, and the parietal and occipital cortices. Further statistical analyses showed that higher complexity values over highly overlapping regions than the ones mentioned above were associated with larger hippocampal volumes only in females. These results suggest that sex differences in healthy aging can be identified from the analysis of magnetoencephalograms with novel signal processing methods.

MeSH Terms

-

Keywords

healthy aging; magnetoencephalography; permutation Lempel-Ziv complexity; sex differences; source space

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.

Abstract

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of HSC aging. In addition, we discuss the potential mechanisms by which HSC aging is regulated.

MeSH Terms

-

Keywords

Aging; HSCs; Replication stress

The association between subjective health perception and lifestyle factors in Shiga prefecture, Japan: a cross-sectional study.

Abstract

The Ministry of Health has reported that in Japan, the Shiga prefecture has the highest life expectancy. Subjective health perception is a predictive indicator of mortality. For this study, we examined the association between subjective health perception and multiple lifestyle factors. Data were obtained from the 2015 Health and Nutrition Survey in Shiga prefecture. The analytic sample comprised 6057 adults aged 20 or older. Information on subjective health perception and lifestyle behaviors was obtained from a self-administered questionnaire. As for subjective health perception, participants were divided into 2 groups: (1) Excellent or Good and (2) Average, Poor, or Very Poor. A 1-day dietary survey was also administered. The health behaviors score (HBS) was calculated based on 5 factors: consuming a healthy diet, never smoking, low-risk alcohol drinking, regular exercise, and moderate sleep duration. HBS scores ranged from 0 to 5. Multiple logistic regression was used to calculate the sex-, age- BMI- and energy intake-adjusted odds ratios (ORs) of poor subjective health across HBS, with 0 points as the reference. Among all participants, 2397 (39.6%) individuals were classified into the good subjective health group. Participants with an HBS of 3 (OR 0.59, 95% CI 0.37-0.96), 4 (OR 0.40, 95% CI 0.24-0.65) or 5 (OR 0.33, 95% CI 0.19-0.59) had a lower OR of rating themselves as being average/poor health compared with those having zero. The association with a higher HBS was remarkable (p for trend: < 0.001). Additional analyses revealed that the combinations including regular exercise were particularly associated with a lower risk of subjective average/poor health. This study showed that the higher the number of healthy lifestyle factors, the lower risk of subjective average/poor health. Combinations of healthy lifestyle factors, especially those involving exercise, suggest good subjective health for individuals living in the Shiga prefecture.

MeSH Terms

-

Keywords

Diet; Lifestyle behavior; Longevity; Subjective health

The optomotor response of aging zebrafish reveals a complex relationship between visual motion characteristics and cholinergic system.

Abstract

Understanding the principles underlying age-related changes in motion perception is paramount for improving the quality of life and health of older adults. However, the mechanisms underlying age-related alterations in this aspect of vision, which is essential for survival in a dynamic world, still remain unclear. Using optomotor responses to drifting gratings, we investigated age-related changes in motion detection of adult zebrafish (wild-type/AB-strain and ache mutants with decreased levels of acetylcholinesterase). Our results pointed out negative optomotor responses that significantly depend on the spatial frequency and contrast level of stimulation, providing supporting evidence for the visual motion-driven aspect of this behavior mainly exhibited by adult zebrafish. Although there were no significant main effects of age and genotype, we found a significant three-way interaction between contrast level, age, and genotype. In the contrast domain, the changes in optomotor responses and thus in the detection of motion direction were age- and genotype-specific. Accordingly, these behavioral findings suggest a strong but complicated relationship between visual motion characteristics and the cholinergic system during neural aging.

MeSH Terms

-

Keywords

Acetylcholine; Aging; Direction; Motion detection; Zebrafish

Global brain volume and N-acetyl-aspartate decline over seven decades of normal aging.

Abstract

We characterize the whole-brain N-acetyl-aspartate (WBNAA) and brain tissue fractions across the adult lifespan and test the hypothesis that, despite age-related atrophy, neuronal integrity (reflected by WBNAA) is preserved in normal aging. Two-hundred-and-seven participants: 133 cognitively intact older adults (73.6 ± 7.4 mean ± standard deviation, range: 60-90 year old) and 84 young (37.9 ± 11, range: 21-59 year old) were scanned with proton magnetic resonance spectroscopy and T -weighted MRI. Their WBNAA, fractional brain parenchyma, and gray and white matter volumes (fBPV, fGM, and fWM) were compared and modeled as functions of age and sex. Compared with young, older-adults' WBNAA was lower by ~35%, and fBPV, fGM and fWM were lower by ~10%. Linear regressions found 0.5%/year WBNAA and 0.2%/year fBPV and fGM declines, whereas fWM rose to age ~40 years, and declined thereafter. fBPV and fGM were 1.8% and 4% higher in women, with no sex decline rates difference. We conclude that contrary to our hypothesis, atrophy was accompanied by WBNAA decline. Across the entire age range, women's brains showed less atrophy than men's. Formulas to estimate WBNAA and brain tissue fractions in healthy adults are provided to help differentiate normal from abnormal aging.

MeSH Terms

-

Keywords

Aging; Atrophy; Brain; MR imaging; MR spectroscopy; N-Acetyl-aspartate

Understanding immunosenescence and its impact on vaccination of older adults.

Abstract

Older adults are more susceptible to viral and bacterial infection, and experience higher incidence and severity of infectious diseases. Although vaccination is the most logical solution in preventing infectious diseases, primary vaccine responses in individuals aged ≥65 years-old fail to generate complete protection. This is presumably attributed to immunosenescence, a term that describes functional differences associated with the immune system and natural age advancement. Both the innate and adaptive immune systems experience age-related impairments that contribute to insufficient protection following vaccination. This review addresses current knowledge of age-related changes that affect vaccine responsiveness; including the deficits in innate cell functions, dampened humoral and cell-mediated immune responses, current vaccination schedules for older adults, and concludes with potential strategies for improving vaccine efficacy specifically for this age group. Due to an age-related decline in immunity and poor vaccine responses, infectious diseases remain a burden among the aged population.

MeSH Terms

-

Keywords

Immune; Older adults; Senescence; Vaccine

Aging in Place With a Spouse in Need: Neighborhood Cohesion and Older Adult Spouses' Physical and Mental Health.

Abstract

This study examines the association of perceived neighborhood cohesion (NC) with older adults' health and the buffering effects of NC against the negative effects of spousal caregiving on health. Data of 3329 community-living older adults living with a spouse in need of care from the Health and Retirement Study were collected at two time-points. Multiple regression analyses were computed for each of the four health outcomes. For men, NC predicted fewer depressive symptoms and better cognition. NC buffered the negative effect of providing activities of daily living (ADL) help to the wife on cognition. For women, NC predicted fewer depressive symptoms and better cognition. NC buffered the negative effect of providing ADL help to the husband on ADL difficulties. The results accentuate the importance of residency location for older adults' physical and mental health. The health benefits of NC may have more implications for older adults providing spousal care.

MeSH Terms

-

Keywords

aging in place; caregiving; neighborhood effects; spouse caregivers

Pelvic floor muscle strength is correlated with sexual function.

Abstract

Sexual performance is related to proprioception and pelvic floor muscle strength (PFMS). The aim of this study was to correlate sexual activity and orgasm with PFMS. A total of 140 healthy continent female were prospectively distributed into 4 groups according to age: Group 1 (G1), 30-40; Group 2 (G2), 41-50; Group 3 (G3), 51-60; Group 4 (G4), over 60 years old. Evaluated parameters were: frequency of sexual activity and orgasm achievement; body mass index (BMI) and objective evaluation of PFMS using perineometer and surface electromyography. BMI was higher in G4 compared to G1 (p=0.042). Women who reported sexual activity was significantly higher in G1 compared to G3 and G4 (94.1% vs. 66.7% and 37.5%, respectively; p=0.001). Orgasm was more frequently in G1 compared to G3 and G4 (91.2% vs. 63.9% and 28.1%, respectively; p=0.001), demonstrating that sexual activity and orgasm decrease after age 51. The duration of PFM contraction was significantly higher in women who had sexual intercourse (p=0.033) and orgasm (p=0.018). Although the frequency of sexual intercourse and orgasm may decrease with aging, a relationship between sexual activity and PFMS remains apparent, once both sexually active women and those who have orgasms showed better PFM endurance than non-sexually active ones.

MeSH Terms

-

Keywords

Aging; Muscle strength dynamometer; Muscular contraction; Sexual activities

The Relevance of Aquaporins for the Physiology, Pathology, and Aging of the Female Reproductive System in Mammals.

Abstract

Aquaporins constitute a group of water channel proteins located in numerous cell types. These are pore-forming transmembrane proteins, which mediate the specific passage of water molecules through membranes. It is well-known that water homeostasis plays a crucial role in different reproductive processes, e.g., oocyte transport, hormonal secretion, completion of successful fertilization, blastocyst formation, pregnancy, and birth. Further, aquaporins are involved in the process of spermatogenesis, and they have been reported to be involved during the storage of spermatozoa. It is noteworthy that aquaporins are relevant for the physiological function of specific parts in the female reproductive system, which will be presented in detail in the first section of this review. Moreover, they are relevant in different pathologies in the female reproductive system. The contribution of aquaporins in selected reproductive disorders and aging will be summarized in the second section of this review, followed by a section dedicated to aquaporin-related proteins. Since the relevance of aquaporins for the male reproductive system has been reviewed several times in the recent past, this review aims to provide an update on the distribution and impact of aquaporins only in the female reproductive system. Therefore, this paper seeks to determine the physiological and patho-physiological relevance of aquaporins on female reproduction, and female reproductive aging.

MeSH Terms

-

Keywords

aging; aquaporin; connexin; female reproductive system; gap-junctions; mammals; ovary; physiology; placenta; uterus

The Role of Nrf2 in D-Galactose-Induced Cardiac Aging in Mice: Involvement of Oxidative Stress.

Abstract

Cardiac aging is the major risk factor for advanced heart disease, which is the leading cause of death in developed countries, accounting for >30% of deaths worldwide. To discover the detailed mechanism of cardiac aging and develop an effective therapeutic candidate drug to treat or delay cardiac aging. We used D-galactose to induce cardiac aging in Nrf2+/+ and Nrf2-/- mice, and then treated these mice with vehicle or the Nrf2 activator, CDDO-imidazolide (CDDO-Im). D-galactose injection significantly induced cardiac aging, cell apoptosis, and oxidative stress in Nrf2+/+ mice, all of which were further exacerbated in Nrf2-/- mice. CDDO-Im treatment can effectively weaken oxidative stress and enhance the activities of antioxidant enzymes, but CDDO-Im lost its antioxidative effect in the Nrf2-/- mice. Nrf2 activator CDDO-Im could therefore effectively protect against D-galactose-induced cardiac aging by inhibiting oxidative stress, suggesting that CDDO-Im might be a potential and promising therapeutic candidate drug to treat cardiac aging.

MeSH Terms

-

Keywords

CDDO-imidazolide; Cardiac aging; D-galactose; Nrf2; Oxidative stress

A recipe for accurate estimation of lifespan brain trajectories, distinguishing longitudinal and cohort effects.

Abstract

We address the problem of estimating how different parts of the brain develop and change throughout the lifespan, and how these trajectories are affected by genetic and environmental factors. Estimation of these lifespan trajectories is statistically challenging, since their shapes are typically highly nonlinear, and although true change can only be quantified by longitudinal examinations, as follow-up intervals in neuroimaging studies typically cover less than 10 % of the lifespan, use of cross-sectional information is necessary. Linear mixed models (LMMs) and structural equation models (SEMs) commonly used in longitudinal analysis rely on assumptions which are typically not met with lifespan data, in particular when the data consist of observations combined from multiple studies. While LMMs require a priori specification of a polynomial functional form, SEMs do not easily handle data with unstructured time intervals between measurements. Generalized additive mixed models (GAMMs) offer an attractive alternative, and in this paper we propose various ways of formulating GAMMs for estimation of lifespan trajectories of 12 brain regions, using a large longitudinal dataset and realistic simulation experiments. We show that GAMMs are able to more accurately fit lifespan trajectories, distinguish longitudinal and cross-sectional effects, and estimate effects of genetic and environmental exposures. Finally, we discuss and contrast questions related to lifespan research which strictly require repeated measures data and questions which can be answered with a single measurement per participant, and in the latter case, which simplifying assumptions that need to be made. The examples are accompanied with R code, providing a tutorial for researchers interested in using GAMMs.

MeSH Terms

-

Keywords

Aging; Cohort effects; Generalized additive mixed models; Lifespan brain research; Longitudinal analysis; MRI; R

Effects of Aging Process on the Damping Performance of ZK60 Magnesium Alloys Prepared by Large Strain Rolling.

Abstract

In this study, the effects of an aging treatment (T5) and a solution + aging treatment (T6) on the microstructure and damping properties of a ZK60 magnesium alloy prepared by large strain rolling (LSR) were studied by an optical microscope (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic thermomechanical analysis (DMA). The results showed that both the T5 and T6 processes had a great impact on the microstructure and damping properties of the ZK60 magnesium alloy. With the increase in aging time, the grain size was basically unchanged, and the amount of the second phase increased, resulting in a gradual decrease in the damping performance. However, compared with the damping performance of the un-aged ZK60 magnesium alloy, the damping performance of the 4 h-aged ZK60 magnesium alloy was enhanced. At the same aging time, the increase in the aging temperature promoted the precipitation of the second phase, thereby reducing the damping performance of the ZK60 magnesium alloy. It was found that the T6-treated ZK60 magnesium alloy had a larger grain size, which led to a better damping performance; in addition, the T6-treated ZK60 magnesium alloy exhibited a damping plateau, which was determined by the distribution and amount of the second phase.

MeSH Terms

-

Keywords

ZK60 magnesium alloy; aging treatment; damping performance; second phase

Nurse Perspectives on Urinary Incontinence in the Home Hospice Setting.

Abstract

To date, no studies have characterized the impacts of urinary incontinence (UI) at the end of life (EOL) in the home hospice (HH) setting. UI is highly prevalent at the EOL and adversely affects quality of life. To characterize HH nurses' perspectives on UI in HH patients. We conducted a qualitative descriptive study of interviews between HH nurses and the study investigator. Thirty-two interviews with HH nurses were transcribed and analyzed. Nurses were mostly female, college-educated, and had several years of experience in HH nursing. We identified findings in four major themes: 1) HH nurses' definition and identification of UI, 2) the absence of formal guidelines for diagnosing UI in HH patients, 3) UI's adverse effect on HH patients and their families, and 4) the lack of standardized guidelines for the management of UI in the HH setting. We found that there was a general lack of clarity on the subtypes of UI and no standardized guidelines for management of UI in the HH setting. Nurses reported that UI was bothersome to HH patients and their caregivers, citing patient discomfort, loss of dignity, and additional labor burden as reasons for this. Management strategies for UI lacked standardization. UI is a prevalent and debilitating condition in HH patients. There is a need for studies to further characterize the impacts of UI on HH patients and their caregivers. Formal training on UI subtypes and management is needed to facilitate proper documentation, research, and improve patient outcomes.

MeSH Terms

-

Keywords

Urinary incontinence; end of life; geriatrics; home hospice; nursing

Female-biased effects of aging on a chimeric hemagglutinin stalk-based universal influenza virus vaccine in mice.

Abstract

To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice. Vaccinated adult mice were better protected than aged mice after challenge with 2009 H1N1 virus, experiencing less morbidity and having lower pulmonary virus titers. The age-associated decline in immunity and protection was consistently greater among females than males, with the reduction in immunity and protection for aged as compared with adult females often being the sole comparison driving the overall age-associated significant differences. The age-associated reduction in stalk-based immunity in females was not, however, associated with changes in estradiol. To determine if the better antibodies in adults could be utilized to protect aged mice, serum was passively transferred from vaccinated adult mice into naïve sex-matched aged mice. Even with transferred serum from young adult mice, aged females still suffered greater morbidity than aged males. These data suggest there are sex-dependent effects of aging on cHA-based universal influenza virus vaccine-induced immunity that cannot be reversed through transfer of serum from young animals. The lack of consideration of sex-specific effects of aging on immunity could hinder efforts toward universal vaccines.

MeSH Terms

-

Keywords

Aging; Estradiol; Flu vaccine; Influenza A virus; Sex difference; Testosterone

Antioxidants N-Acetylcysteine and Vitamin C Improve T Cell Commitment to Memory and Long-Term Maintenance of Immunological Memory in Old Mice.

Abstract

Aging is characterized by reduced immune responses, a process known as immunosenescence. Shortly after their generation, antigen-experienced adaptive immune cells, such as CD8 and CD4 T cells, migrate into the bone marrow (BM), in which they can be maintained for long periods of time within survival niches. Interestingly, we recently observed how oxidative stress may negatively support the maintenance of immunological memory in the BM in old age. To assess whether the generation and maintenance of immunological memory could be improved by scavenging oxygen radicals, we vaccinated 18-months (old) and 3-weeks (young) mice with alum-OVA, in the presence/absence of antioxidants vitamin C (Vc) and/or N-acetylcysteine (NAC). To monitor the phenotype of the immune cell population, blood was withdrawn at several time-points, and BM and spleen were harvested 91 days after the first alum-OVA dose. Only in old mice, memory T cell commitment was boosted with some antioxidant treatments. In addition, oxidative stress and the expression of pro-inflammatory molecules decreased in old mice. Finally, changes in the phenotype of dendritic cells, important regulators of T cell activation, were additionally observed. Taken together, our data show that the generation and maintenance of memory T cells in old age may be improved by targeting oxidative stress.

MeSH Terms

-

Keywords

NAC; T cells; aging; antioxidants; immunosenescence; vaccination; vitamin C

Serum soluble Klotho is inversely related to coronary artery calcification assessed by intravascular ultrasound in patients with stable coronary artery disease.

Abstract

Although the Klotho gene is recognized as an aging-suppressor gene, the clinical significance of its soluble product, soluble Klotho, in coronary artery disease (CAD) has not been completely determined. The relationship between soluble Klotho and coronary artery calcification (CAC) was investigated in patients with stable CAD. CAC in culprit lesions was analyzed in 75 non-dialysis patients with stable CAD who were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). The main outcome measure was the calcium index (CalcIndex), a volumetric IVUS-derived measure of total calcification per culprit lesion. A low CalcIndex was defined as a first-quartile calcium index (<0.042). Patients were divided into two groups according to the median serum Klotho value: low Klotho (n = 37, ≤460 pg/mL) and high Klotho (n = 38, >460 pg/mL). The CalcIndex was significantly lower in patients with high than with low Klotho. Patients with high Klotho had a significantly higher prevalence of a low CalcIndex than those with low Klotho. The number of angiographic moderate-severe CACs in whole coronary arteries was significantly decreased in patients with high Klotho compared to low Klotho. Serum Klotho levels correlated significantly and inversely with the CalcIndex. This relationship was pronounced in patients with estimated glomerular filtration rate <60 mL/min/1.73 m . Logistic regression analysis showed that high Klotho was associated with a low CalcIndex independent of classical coronary risk factors and markers of mineral metabolism. High serum soluble Klotho levels are associated with a low degree of CAC in non-dialysis, stable CAD patients treated by PCI.

MeSH Terms

-

Keywords

Aging; Coronary artery calcification; Intravascular ultrasound; Klotho

Psychological Distress After Covid-19 Recovery: Reciprocal Effects With Temperament and Emotional Dysregulation. An Exploratory Study of Patients Over 60 Years of Age Assessed in a Post-acute Care Service.

Abstract

To study the long-term psychological effects of Covid-19 disease, we recruited 61 patients older than 60 years of age and administered the Kessler questionnaire K10 to assess psychological distress and classify them according to mental health risk groups. Patients' affective temperaments were assessed with the 39-item form of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A-39) and emotional dysregulation with the Difficulties in Emotion Regulation Scale (DERS). Patients were divided in two samples according to their scores on the K10, i.e., a high likelihood of psychological distress group ([i]N[/i] = 18) and a low likelihood of psychological distress group ([i]N[/i] = 43). The two groups differed on their gender composition, in that more women ([i]N[/i] = 11) were in the former and more men in the latter ([i]N[/i] = 29) (χ = 4.28; [i]p[/i] = 0.039). The high likelihood of psychological distress group scored higher on the Cyclothymic (3.39 ± 3.45 vs. 0.93 ± 1.08, [i]p[/i] < 0.001) and the Depressive (2.28 ± 2.82 vs. 0.65 ± 1.09, [i]p[/i] = 0.01) affective temperaments of the TEMPS and on the lack of Impulse control (12.67 ± 4.04 vs. 9.63 ± 3.14, [i]p[/i] = 0.003) and lack of Clarity (15.00 ± 5.56 vs. 9.85 ± 4.67, [i]p[/i] = 0.004) scales of the DERS. Our results show that having had Covid-19 may be related with high likelihood for psychological distress in advanced-age people and this may in turn be associated with impaired emotional regulation and higher scores on depressive and cyclothymic temperaments.

MeSH Terms

-

Keywords

COVID-19; affective temperaments; aging; emotional dysregulation; nasal swab; nasopharyngeal swab; psychological distress

The cellular mechanobiology of aging: from biology to mechanics.

Abstract

Aging is a chronic, complicated process that leads to degenerative physical and biological changes in living organisms. Aging is associated with permanent, gradual physiological cellular decay that affects all aspects of cellular mechanobiological features, including cellular cytoskeleton structures, mechanosensitive signaling pathways, and forces in the cell, as well as the cell's ability to sense and adapt to extracellular biomechanical signals in the tissue environment through mechanotransduction. These mechanobiological changes in cells are directly or indirectly responsible for dysfunctions and diseases in various organ systems, including the cardiovascular, musculoskeletal, skin, and immune systems. This review critically examines the role of aging in the progressive decline of the mechanobiology occurring in cells, and establishes mechanistic frameworks to understand the mechanobiological effects of aging on disease progression and to develop new strategies for halting and reversing the aging process. Our review also highlights the recent development of novel bioengineering approaches for studying the key mechanobiological mechanisms in aging.

MeSH Terms

-

Keywords

aging; cytoskeleton; force; mechanobiology; mechanotransduction

Dysregulation of leukocyte trafficking in ageing: Causal factors and possible corrective therapies.

Abstract

Ageing is a universal biological phenomenon that is accompanied by the development of chronic, low-grade inflammation and remodelling of the immune system resulting in compromised immune function. In this review, we explore how the trafficking of innate and adaptive immune cells under homeostatic and inflammatory conditions is dysregulated in ageing. We particularly highlight the age-related changes in the expression of adhesion molecules and chemokine receptor/ligands, and the accumulation of senescent cells that drive modulated leukocyte trafficking. These age-related changes to leukocyte trafficking are multifactorial and specific to leukocyte subsets, tissue, type of vascular beds, and inflammatory status. However, dysregulated leukocyte trafficking ultimately affects immune responses in older adults. We therefore go on to discuss approved drugs, including anti-integrins, anti-chemokines and statins, as well as novel therapeutics that may be used to target dysregulated leukocyte trafficking in ageing, improve immune responses and delay the onset of age-related diseases.

MeSH Terms

-

Keywords

Leukocyte; ageing; inflammageing; senescence; therapies; trafficking

Adaptation of the comprehensive geriatric assessment to a virtual delivery format.

Abstract

---

MeSH Terms

-

Keywords

geriatric assessment; geriatrics; telehealth; telemedicine

Alkaline ceramidase family: The first two decades.

Abstract

Ceramidases are a group of enzymes that catalyze the hydrolysis of ceramide, dihydroceramide, and phytoceramide into sphingosine (SPH), dihydrosphingosine (DHS), and phytosphingosine (PHS), respectively, along with a free fatty acid. Ceramidases are classified into the acid, neutral, and alkaline ceramidase subtypes according to the pH optima for their catalytic activity. YPC1 and YDC1 were the first alkaline ceramidase genes to be identified and cloned from the yeast Saccharomyces cerevisiae two decades ago. Subsequently, alkaline ceramidase genes were identified from other species, including one Drosophila melanogaster ACER gene (Dacer), one Arabidopsis thaliana ACER gene (AtACER), three Mus musculus ACER genes (Acer1, Acer2, and Acer3), and three Homo sapiens ACER genes (ACER1, ACER2, and ACER3). The protein products of these genes constitute a large protein family, termed the alkaline ceramidase (ACER) family. All the biochemically characterized members of the ACER family are integral membrane proteins with seven transmembrane segments in the Golgi complex or endoplasmic reticulum, and they each have unique substrate specificity. An increasing number of studies suggest that the ACER family has diverse roles in regulating sphingolipid metabolism and biological processes. Here we discuss the discovery of the ACER family, the biochemical properties, structures, and catalytic mechanisms of its members, and its role in regulating sphingolipid metabolism and biological processes in yeast, insects, plants, and mammals.

MeSH Terms

-

Keywords

Aging; Alkaline ceramidase; Cancer; Inflammation; Neurodegeneration; Placenta; Reproduction; Skin; Sphingolipids; Stress response

Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis.

Abstract

Intervertebral disc degeneration (IDD) represents major cause of low back pain. Quercetin (QUE) is one of the approved senolytic agents. In this study, we evaluated the protective effects of QUE on IDD development and its underlying mechanism. Effects of senolytic agent QUE on the viability of nucleus pulposus cells (NPCs) were measured by CCK-8 assays and EdU staining. The senescence associated secreted phenotype (SASP) factors expressions were measured by qPCR, western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and western blot. Molecular docking was applied to predict the interacting protein of QUE; while Nrf2 was knocked down by siRNAs to confirm its role in QUE regulated senescence phenotype. X-ray, MRI, Hematoxylin-Eosin and Safranin O-Fast green staining were performed to evaluate the therapeutic effects of QUE on IDD in the puncture-induced rat model. In in vitro experiments, QUE inhibited SASP factors expression and senescence phenotype in IL-1β-treated NPCs. Mechanistically, QUE suppressed IL-1β induced activation of the NF-κB pathway cascades; it was also demonstrated in molecular docking and knock down studies that QUE might bind to Keap1-Nrf2 complex to suppress NF-κB pathway. In vivo, QUE ameliorated the IDD process in the puncture-induced rat model. Together the present work suggests that QUE inhibits SASP factors expression and senescence phenotype in NPCs and ameliorates the progression of IDD via the Nrf2/NF-κB axis, which supports senolytic agent QUE as a potential therapeutic agent for the treatment of IDD.

MeSH Terms

-

Keywords

Intervertebral disc degeneration; NF-κB pathway; Nrf2; Quercetin; Senescence

[i]Lactobacillus plantarum[/i] DR7 improved brain health in aging rats via the serotonin, inflammatory and apoptosis pathways.

Abstract

Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of [i]Lactobacillus plantarum[/i] DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and [i]L. plantarum[/i] DR7 (10 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats ([i]P[/i]<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of [i]L. plantarum[/i] DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of [i]L. plantarum[/i] DR7 as a prospective dietary strategy to improve cognitive functions during aging.

MeSH Terms

-

Keywords

Lactobacillus spp.; aging; brain

Investigation on Microstructures and Mechanical Properties of Isotactic Polypropylene Parts Fabricated by Different Process Conditions with Different Aging Periods.

Abstract

Polymeric parts have been increasingly used in various engineering fields. The performance of polymeric parts is significantly affected by working-environment-induced aging. In this paper, an ultrasonic-vibration-assisted injection molding system was designed and utilized to fabricate polymeric parts from isotactic polypropylene (iPP) using different processing conditions. The natural aging experiments were performed to age the fabricated iPP parts for one year. The effects of key process parameters as well as ultrasound power on the microstructures and the mechanical properties of the iPP parts after aging were systematically investigated using X-ray diffraction analysis, Fourier transform infrared analysis, scanning electron microscope imaging, and tensile testing. It is found that both the microstructures and the tensile strength of the iPP parts deteriorate with the increasing aging time. In addition, the crystallinity and the tensile strength decrease with the increasing melt temperature but increase with the increasing mold temperature in a given range and holding pressure. The increase in ultrasound power leads to an increase in crystallinity. However, when the ultrasound power is over 200 W, the tensile strength of the aged iPP parts decreases, which indicates that high ultrasound power may not form optimal condensed microstructures with excellent anti-aging capacity.

MeSH Terms

-

Keywords

condensed microstructures; natural aging experiments; process parameters; tensile strength; ultrasound vibration

The Epidemiological Characteristics of Late-Onset Hypogonadism in Chinese Middle-Aged and Elderly Men: Two Cross-Sectional Studies in the Same Community.

Abstract

The purpose of this study was to investigate the prevalence and epidemiological characteristics of late-onset hypogonadism (LOH) in middle-aged and elderly Chinese men. Two cross-sectional studies were conducted at 5-year intervals in community-dwelling men living in the same area. A total of 1472 (Study 1, S1) and 944 (Study 2, S2) men aged 40-69 years old were recruited as subjects. Subjects were evaluated through combining serum reproductive hormone levels with the Androgen Deficiency in Aging Males (ADAM) questionnaire and the Aging Males' Symptoms (AMS) scale. A significant difference was found in mean testosterone deficiency (TD) prevalence between S1 and S2, using either serum total testosterone (TT; 14.02% vs. 6.36%) or serum calculated free testosterone (cFT; 43.69% vs. 16.53%) cutoff values. According to the S1 or S2 data, the mean prevalence of LOH was 37.85%/15.47% in the positive ADAM test and 15.42%/9.43% in the positive AMS test ([i]p[/i] < .01). According to classifications of TD based on gonadal status, the prevalence of secondary TD (27.34%) was higher than the primary (16.36%) and compensated (15.42%) TD in S1 ([i]p[/i] < .01). However, there were significant differences among the prevalence of primary (6.89%), secondary (9.64%), and compensated (27.65%) TD in S2 ([i]p[/i] < .05). Different types of testosterone levels, TD cutoff values, and questionnaires influenced the prevalence of TD and LOH. The serum FT cutoff value was an optimal threshold for evaluating and diagnosing TD and LOH, whose prevalence increased gradually with male aging.

MeSH Terms

-

Keywords

aging; epidemiology; hypogonadism; male; prevalence; testosterone

Role of nutraceuticals in cognition during aging and related disorders.

Abstract

Cognitive abilities are compromised with advancing age posing a great risk for the development of dementia and other related brain disorders. Genetic susceptibility as well as environmental exposures determine the fate of cognitive aging and its transition to pathological states. Emerging epidemiological and observational studies have revealed the importance of lifestyle factors including dietary patterns and nutritional intake in the maintenance of cognitive health and reducing the risk of neurodegenerative disorders. In this context, nutraceutical interventions have gained considerable attention in preventing age-related cognitive deficits and counteracting pathological processes. Nutraceuticals include dietary plants and derivatives, food supplements and processed foods with nutritional and pharmaceutical values. The present review highlights the importance of nutraceuticals in attenuating cognitive aging and its progression to dementia, with specific emphasis on chemical constituents, neurocognitive properties and mechanism of action.

MeSH Terms

-

Keywords

Aging; Cognition; Dementia; Dietary supplements; Nutrition; Phytochemicals

The proteasome: friend and foe of mitochondrial biogenesis.

Abstract

Most mitochondrial proteins are synthesized in the cytosol and subsequently translocated as unfolded polypeptides into mitochondria. Cytosolic chaperones maintain precursor proteins in an import-competent state. This post-translational import reaction is under surveillance of the cytosolic ubiquitin-proteasome system, which carries out several distinguishable activities. On the one hand, the proteasome degrades nonproductive protein precursors from the cytosol and nucleus, import intermediates that are stuck in mitochondrial translocases, and misfolded or damaged proteins from the outer membrane and the intermembrane space. These surveillance activities of the proteasome are essential for mitochondrial functionality, as well as cellular fitness and survival. On the other hand, the proteasome competes with mitochondria for nonimported cytosolic precursor proteins, which can compromise mitochondrial biogenesis. In order to balance the positive and negative effects of the cytosolic protein quality control system on mitochondria, mitochondrial import efficiency directly regulates the capacity of the proteasome via transcription factor Rpn4 in yeast and nuclear respiratory factor (Nrf) 1 and 2 in animal cells. In this review, we provide a thorough overview of how the proteasome regulates mitochondrial biogenesis.

MeSH Terms

-

Keywords

Rpn4; aging; mitochondria; mitochondria-associated degradation; mitoprotein-induced stress response; proteasome; protein degradation; protein quality control; ubiquitin

Epidemiology of geriatric trauma patients in Norway: A nationwide analysis of Norwegian Trauma Registry data, 2015-2018. A retrospective cohort study.

Abstract

Geriatric patients have a high risk of poor outcomes after trauma and is a rapid-increasing group within the trauma population. Given the need to ensure that the trauma system is targeted, efficient, accessible, safe and responsive to all age groups the aim of the present study was to explore the epidemiology and characteristics of the Norwegian geriatric trauma population and assess differences between age groups within a national trauma system. This retrospective analysis is based on data from the Norwegian Trauma Registry (2015-2018). Injury severity was scaled using the Abbreviated Injury Scale (AIS), and the New Injury Severity Score (NISS). Trauma patients 16 years or older with NISS ≥9 were included, dichotomized into age groups 16-64 years (Group 1, G1) and ≥65 years (Group 2, G2). The groups were compared with respect to differences in demographics, injury characteristics, management and outcome. Descriptive statistics and relevant parametric and non-parametric tests were used. Geriatric patients proved to be at risk of sustaining severe injuries. Low-energy falls predominated in G2, and the AIS body regions 'Head' and 'Pelvis and lower extremities' were most frequently injured. Crude 30-day mortality was higher in G2 compared to G1 (G1: 2.9 vs. G2: 13.6%, P<0.01) and the trauma team activation (TTA) rate was lower (G1: 90 vs. G2: 73%, P<0.01). A lower proportion of geriatric patients were treated by a physician prehospitally (G1: 30 vs. G2: 18%, [NISS 15-24], P<0.01) and transported by air-ambulance (G1: 24 vs. G2: 14%, [NISS 15-24], P<0.01). Median time from alarm to hospital admission was longer for geriatric patients (G1: 71 vs. G2: 78 min [NISS 15-24], P<0.01), except for the most severely injured patients (NISS≥25). In this nationwide study comparing adult and geriatric trauma patients, geriatric patients were found to have a higher mortality, receive less frequently advanced prehospital treatment and transportation, and a lower TTA rate. This is surprising in the setting of a Nordic country with free access to publicly funded emergency services, a nationally implemented trauma system with requirements to pre- and in-hospital services and a national trauma registry with high individual level coverage from all trauma-receiving hospitals. Further exploration and a deeper understanding of these differences is warranted.

MeSH Terms

-

Keywords

Aging; Elderly; Epidemiology; Geriatric; Injury severity score; Major trauma; Multiple trauma; Older adults; Quality of health care; Trauma registries; Traumatic

Cognitive decline in older adults with epilepsy: The Cardiovascular Health Study.

Abstract

Cognitive decline is a major concern for older adults with epilepsy. Whether and how much faster older adults with epilepsy experience cognitive decline beyond expected age-related cognitive change remain unclear. We sought to estimate and compare rates of cognitive decline in older adults with and without epilepsy. The Cardiovascular Health Study is a population-based longitudinal cohort study of 5888 US adults aged 65+. Cognitive function was assessed annually with Modified Mini-Mental State Exam (3MS) and Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate average rates of decline in 3MS and DSST scores by epilepsy status (prevalent, incident, or no epilepsy), adjusted for risk factors associated with cognitive decline. The rate of decline in 3MS was significantly faster in prevalent epilepsy (P < .001) and after incident epilepsy (P = .002) compared with no epilepsy. Prevalent epilepsy and apolipoprotein E gene (APOE) ε4 (ApoE4) had a synergistic interaction, whereby prevalent epilepsy and ApoE4 together were associated with 1.51 points faster annual decline in 3MS than would be expected if prevalent epilepsy and ApoE4 did not interact (P < .001). Older adults with prevalent epilepsy had a significantly lower initial DSST score and faster rate of decline compared to those with no epilepsy (P < .001). Faster decline in global cognitive ability seen in this study validates concerns of patients. ApoE4 allele status was an effect modifier of the relationship between cognitive decline and prevalent epilepsy. Further research is warranted to explore biological mechanisms and possible interventions to mitigate cognitive decline.

MeSH Terms

-

Keywords

all epilepsy/seizures; cognitive aging; cohort studies; natural history studies (prognosis)

The role of cap-dependent translation in aged-related changes in neuroimmunity and affective behaviors.

Abstract

Translation regulation in the context of aged-associated inflammation and behavioral impairments is not well characterized. Aged individuals experience lower life quality due to behavioral impairments. In this study, we used young and aged transgenic mice that are unable to activate the cap-binding protein, eukaryotic translation initiation factor 4E (eIF4E) to examine the role of protein translation control in aging, memory, depression, and anxiety. To determine how products of cap-dependent translation play a permissive role in aged-associated inflammation, we assessed levels of pro-inflammatory cytokines in various brain regions involved in the above-mentioned behaviors. We found that functional eIF4E is not necessary for age-related deficits in spatial and short-term memory but is important for depressive and anxiety-like behavior and this is correlated with pro-inflammatory cytokines in discrete brain regions. Thus, we have begun to elucidate a role for eIF4E phosphorylation in the context of aged-related behavioral impairments and chronic low-grade inflammation that may help identify novel immune modulators for therapeutic targets and decrease the burden of self-care among the geriatric population.

MeSH Terms

-

Keywords

Aging; Anxiety; Cognition; Depression; Inflammation; eIF4E

Distinct Age-Related Epigenetic Signatures in CD4 and CD8 T Cells.

Abstract

Healthy immune aging is in part determined by how well the sizes of naïve T cell compartments are being maintained with advancing age. Throughout adult life, replenishment largely derives from homeostatic proliferation of existing naïve and memory T cell populations. However, while the subpopulation composition of CD4 T cells is relatively stable, the CD8 T cell compartment undergoes more drastic changes with loss of naïve CD8 T cells and accumulation of effector T cells, suggesting that CD4 T cells are more resilient to resist age-associated changes. To determine the epigenetic basis for these differences in behaviors, we compared chromatin accessibility maps of CD4 and CD8 T cell subsets from young and old individuals and related the results to the expressed transcriptome. The dominant age-associated signatures resembled hallmarks of differentiation, which were more pronounced for CD8 naïve and memory than the corresponding CD4 T cell subsets, indicating that CD8 T cells are less able to keep cellular quiescence upon homeostatic proliferation. In parallel, CD8 T cells from old adults, irrespective of their differentiation state, displayed greater reduced accessibility to genes of basic cell biological function, including genes encoding ribosomal proteins. One possible mechanism is the reduced expression of the transcription factors YY1 and NRF1. Our data suggest that chromatin accessibility signatures can be identified that distinguish CD4 and CD8 T cells from old adults and that may confer the higher resilience of CD4 T cells to aging.

MeSH Terms

-

Keywords

T-cell; T-cell homeostasis; aging; chromatin accessibility; epigenetics; ribosomal proteins

Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK CD8 T Cells as Conserved Hallmark of Inflammaging.

Abstract

Systematic understanding of immune aging on a whole-body scale is currently lacking. We characterized age-associated alterations in immune cells across multiple mouse organs using single-cell RNA and antigen receptor sequencing and flow cytometry-based validation. We defined organ-specific and common immune alterations and identified a subpopulation of age-associated granzyme K (GZMK)-expressing CD8 T (Taa) cells that are distinct from T effector memory (Tem) cells. Taa cells were highly clonal, had specific epigenetic and transcriptional signatures, developed in response to an aged host environment, and expressed markers of exhaustion and tissue homing. Activated Taa cells were the primary source of GZMK, which enhanced inflammatory functions of non-immune cells. In humans, proportions of the circulating GZMK CD8 T cell population that shares transcriptional and epigenetic signatures with mouse Taa cells increased during healthy aging. These results identify GZMK Taa cells as a potential target to address age-associated dysfunctions of the immune system.

MeSH Terms

-

Keywords

Aging; CD8 T cells; CITE-seq; granzyme K; immune system; inflammaging; single-cell ATAC-sequencing; single-cell BCR-sequencing; single-cell RNA-sequencing; single-cell TCR-sequencing

Effects of Blood Pressure on Cognitive Performance in Aging: A Systematic Review.

Abstract

Cognitive functions play a crucial role in daily functioning. Unfortunately, some cognitive abilities decline in the process of healthy aging. An increasing body of evidence has highlighted the role of lifestyle habits and cardiovascular diseases, such as high blood pressure, in increasing the risk of cognitive decline. Surprisingly, although hypertension is a modifiable risk factor for cerebrovascular damage, the role of hypertension on cognitive impairment development is not still clear. Several key questions remain unresolved, and there are many inconsistent results in studies considering this topic. This review is aimed to systematically analyze the results found by the studies that investigated whether high blood pressure, in both hypertensive and healthy people, is related to cognitive performance. Furthermore, it points to evaluate the role of age in this relationship. [i]Method:[/i] The review process was conducted according to the PRISMA statement. Restrictions were made, selecting the studies in English and published in peer-review journals, including at least one cognitive measure and blood pressure measurement. Studies that included participants with medical conditions, dementia, psychiatric disorders, strokes, and brain injury were excluded. Cross-sectional and longitudinal studies were analyzed separately. Finally, blood pressure measured at young life (18-39 years), midlife (age 40-64 years), elderly (65-74 years), and old age (≥75 years) were considered. [i]Results:[/i] The review allows 68 studies to be selected, which include 154,935 participants. The results provided evidence of an adverse effect of exposure to high blood pressure on cognitive performance. High blood pressure in midlife was linked with poorer cognitive functioning; this evidence was found in cross-sectional and longitudinal studies. However, this association declines with increasing age and tends to become inconsistent. In older people, the relationship between blood pressure and cognitive performance is non-linear, highlighting a beneficial effect of high blood pressure on cognition. [i]Conclusions:[/i] Despite some limitations, this review showed that cardiovascular and neuro-cognitive systems do not operate in isolation, but they are related. Blood pressure can be considered an early biomarker of cognitive impairment, and the necessity of early blood pressure measurement and control was underlined.

MeSH Terms

-

Keywords

aging; blood pressure; cognitive functions; cognitive impairment; hypertension; review

Psychosocial Factors Associated with Cognitive Function Among Middle-Aged and Older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos and its Sociocultural Ancillary Study.

Abstract

Evidence suggests that psychosocial factors are associated with cognitive health in older adults; however, associations of psychosocial factors with cognition remain largely unexamined in middle-aged and older Hispanics/Latinos. To examine the cross-sectional associations of psychosocial factors with cognitive function among middle-aged and older Hispanics/Latinos living in the US. Baseline (2008-2011) data from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (n = 2,818; ages 45-74) were used to examine the associations of each psychosocial factor with global cognition (GC), verbal learning, verbal memory, verbal fluency, and processing speed independent of age, sex, education, Hispanic/Latino background, income, language, and depressive symptoms. Psychosocial variables included: intrapersonal factors (ethnic identity, optimism, and purpose in life), interpersonal factors (family cohesion, familism, social network embeddedness, and social support), and social stressors (perceived ethnic discrimination, loneliness, and subjective social status). In fully-adjusted models, purpose in life and social support were each positively associated with all five cognitive variables. Loneliness was negatively associated with GC, verbal learning, memory, and processing speed. Ethnic identity was positively and familism negatively associated with GC, verbal fluency, and processing speed. Family cohesion was positively associated with verbal learning. These findings extend previous evidence from older, largely non-Hispanic White cohorts to show that higher purpose in life and social support are also strongly associated with cognitive health among middle-aged and older Hispanics/Latinos. We also highlight that intrapersonal factors, interpersonal factors, and social stressors have differential relationships with individual cognitive tests.

MeSH Terms

-

Keywords

Cognitive aging; Hispanics; Latinos; cognitive function; psychosocial factors

The Geriatric Feelings of Burdensomeness Scale (GFBS).

Abstract

The present article describes the development and psychometric evaluation of the Geriatric Feelings of Burdensomeness Scale using two samples of older adults collected through Amazon Mechanical Turk. The scale is a 25-item measure of general subjective feeling of being a burden on or problem for others. The goal of the measure is to capture a broad conceptualization of burdensomeness that is relevant to a variety of important psychological variables.  : Two studies are described, including item development and selection, and the examination of reliability and validity evidence in a sample of 192 older adults.  : The estimates of reliability (coefficient alpha and average interitem correlations) were strong. Preliminary examination of convergent validity evidence found significant moderate correlations between the Geriatric Feelings of Burdensomeness Scale and measures of conceptually related constructs (hopelessness, suicidality, perceived burdensomeness, thwarted belongingness). Small, non-significant correlations were found between three indices of religiosity, providing preliminary discriminant validity evidence.  : Our results provide initial psychometric support for a more general and inclusive assessment tool for measuring older adults' feelings of burdensomeness.  : With further research on clinical significance of feelings of burdensomeness and predictive validity, this measure may be used to identify concerns and beliefs about burdensomeness among distressed older adults.

MeSH Terms

-

Keywords

Older adults; aging; assessment; burden; measurement; mental health

Can Serum Nitrosoproteome Predict Longevity of Aged Women?

Abstract

Aging is characterized by increase in reactive oxygen (ROS) and nitrogen (RNS) species, key factors of cardiac failure and disuse-induced muscle atrophy. This study focused on serum nitroproteome as a trait of longevity by adopting two complementary gel-based techniques: two-dimensional differential in gel electrophoresis (2-D DIGE) and Nitro-DIGE coupled with mass spectrometry of albumin-depleted serum of aged (A, [i]n[/i] = 15) and centenarian (C, [i]n[/i] = 15) versus young females (Y, [i]n[/i] = 15). Results indicate spots differently expressed in A and C compared to Y and spots changed in A vs. C. Nitro-DIGE revealed nitrosated protein spots in A and C compared to Y and spots changed in A vs. C only ([i]p[/i]-value < 0.01). Nitro-proteoforms of alpha-1-antitripsin (SERPINA1), alpha-1-antichimotripsin (SERPINA3), ceruloplasmin (CP), 13 proteoforms of haptoglobin (HP), and inactive glycosyltransferase 25 family member 3 (CERCAM) increased in A vs. Y and C. Conversely, nitrosation levels decreased in C vs. Y and A, for immunoglobulin light chain 1 (IGLC1), serotransferrin (TF), transthyretin (TTR), and vitamin D-binding protein (VDBP). Immunoblottings of alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR) and thioredoxin reductase 1 (TRXR1) indicated lower levels of ADH5 in A vs. Y and C, whereas TRXR1 decreased in A and C in comparison to Y. In conclusion, the study identified putative markers in C of healthy aging and high levels of ADH5/GSNOR that can sustain the denitrosylase activity, promoting longevity.

MeSH Terms

-

Keywords

aging; cardiovascular disease; muscle atrophy; nitrosative stress; proteomics

[The age-related positivity effect: forgetting the negative and/or remembering the positive? An inter-task study].

Abstract

A growing number of studies have shown that, compared to young adults, older adults better remember positive information than negative information. However, it is not clear whether this age-related positivity effect relies on an increase in positive information memory and/or on a decrease in negative information memory. Thus, we aimed to study the specific mechanisms underlying the age-related positivity effect in different memory tasks. To do so, we used an emotional word memory paradigm including immediate free recall, recognition and delayed free recall tasks. Forty-five young adults (m = 20.0 years) and 45 older adults (m = 69.2 years) native French speakers participated. Thirty-six low French words, including 12 negative (e.g. égout), 12 positive (e.g. lagune) and 12 neutral (e.g. notion) words were selected from an emotional lexical database (Gobin et al. 2017). For the recognition task, 36 new words were selected. The results showed that the age-related positivity effect specifically depended on a decrease in negativity preference (i.e. the comparison between negative and neutral words) in older adults, in comparison with young adults, both in immediate and delayed free recall tasks. Indeed, in these tasks, young adults recalled more negative than neutral words whereas there was no difference in older adults. In recognition task, no age-related positivity effect has been observed. Moreover, the results showed that, in immediate recall, the higher the older adults memory abilities, the lower their negativity preference. This correlation was not significant in delayed recall. These results suggest that, when compared with young adults, older adults disengage from negative words processing through costly cognitive processes. A small magnitude of negativity preference would indicate good maintenance of memory abilities. Results are discussed in the framework of the socioemotional selectivity theory.

MeSH Terms

-

Keywords

aging; emotion; memory; positivity effect

Association between brain volumes and patterns of physical activity in community-dwelling older adults.

Abstract

Larger brain volumes are often associated with more free-living physical activity (PA) in cognitively normal older adults. Yet, whether greater brain volumes are associated with more favorable (less fragmented) PA patterns, and whether this association is stronger than with total PA, remains unknown. Brain magnetic resonance imaging and wrist-worn accelerometer data were collected in 301 participants (mean age=77[SD=7] years, 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Linear regression models were fit to examine whether brain volumes (cc) were cross-sectionally associated with: 1) total daily PA minutes; and 2) activity fragmentation (mean number of PA bouts / total PA minutes x 100). Sensitivity analyses were conducted by adjusting for counterpart PA variables (e.g., fragmentation covariate included in the PA minutes model). Greater white matter volumes in the parietal and temporal lobes were associated with higher daily PA minutes (2.6(SE=1.0) and 3.8(0.9)min/day, respectively; p<0.009 for both) after adjusting for demographics, behavioral factors, medical conditions, gait speed, apolipoprotein E e4 status, and intracranial volume. Greater temporal white matter volume was associated with lower fragmentation (-0.16(0.05)%, p=0.003). In sensitivity analyses, observed associations between brain volumes and daily PA minutes remained significant while associations with fragmentation no longer remained significant. Our results suggest white matter brain structure in cognitively normal older adults is associated with the total amount of PA and, to a lesser extent, the PA accumulation patterns. More work is needed to elucidate the longitudinal relationship between brain structure and function and PA patterns with aging.

MeSH Terms

-

Keywords

Aging; brain structure; fragmentation; total activity; white matter

Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis.

Abstract

Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age-dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age-related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age-related anxiety-like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation.

MeSH Terms

-

Keywords

adult hippocampal neurogenesis; lamin B1; mood regulation; stem cell aging

Retention Forces of Prosthetic Clasps over a Simulated Wearing Period of Six Years In-Vitro: Direct Metal Laser Melting Versus Dental Casting.

Abstract

This study determinates the persistence of retention force in Akers-clasps for removable partial dentures made from Co-Cr alloy. Therefore, standardized computer-aided designed (CAD) clasp #1 specimens were made by direct metal laser melting (DMLM, n = 10) and by lost-wax dental casting (DC) of computer-aided manufactured (CAM) replicas (n = 10, DC) from two comparable Co-Cr alloys. The retention force was tested after manufacturing for 9000 cycles of setting and removal from a molar tooth crown analog made from zirconia; simulating in-vitro a duration of six years in service. The first and last 360 cycles (T0 and T1, 3 months each) of all specimens were selected for comparison of retention forces between the materials. A constant decrease of 6% from the initial retention force (T0 = 4.86 N, SD = 0.077; T1 = 4.57 N, SD = 0.037) was detected at the DC specimens, and an increase of 4% in DMLM specimens (T0 = 5.69 N, SD = 0.078; T1 = 5.92 N, SD = 0.077); all differences were statistically significant ([i]p[/i] < 0.0001). Even if these deviations are not of clinical relevance, further studies and applications should investigate the fatigue behavior of laser melted Co-Cr-alloys for dental application.

MeSH Terms

-

Keywords

additive manufacturing; ageing; dental prosthesis; longevity; non-precious alloy

Refined Multiscale Fuzzy Entropy to Analyse Post-Exercise Cardiovascular Response in Older Adults With Orthostatic Intolerance.

Abstract

Orthostatic intolerance syndrome occurs when the autonomic nervous system is incapacitated and fails to respond to the demands associated with the upright position. Assessing this syndrome among the elderly population is important in order to prevent falls. However, this problem is still challenging. The goal of this work was to determine the relationship between orthostatic intolerance (OI) and the cardiovascular response to exercise from the analysis of heart rate and blood pressure. More specifically, the behavior of these cardiovascular variables was evaluated in terms of refined composite multiscale fuzzy entropy (RCMFE), measured at different scales. The dataset was composed by 65 older subjects, 44.6% ([i]n[/i] = 29) were OI symptomatic and 55.4% ([i]n[/i] = 36) were not. Insignificant differences were found in age and gender between symptomatic and asymptomatic OI participants. When heart rate was evaluated, higher differences between groups were observed during the recovery period immediately after exercise. With respect to the blood pressure and other hemodynamic parameters, most significant results were obtained in the post-exercise stage. In any case, the symptomatic OI group exhibited higher irregularity in the measured parameters, as higher RCMFE levels in all time scales were obtained. This information could be very helpful for a better understanding of cardiovascular instability, as well as to recognize risk factors for falls and impairment of functional status.

MeSH Terms

-

Keywords

aging; blood pressure; exercise; hear rate; orthostatic intolerance; refined composite multiscale fuzzy entropy

Ultrasonography Shows Age-related Changes and Related Factors in the Tongue and Suprahyoid Muscles.

Abstract

To investigate age and other factors related to the deterioration of the muscles used for swallowing, including the tongue and suprahyoid muscles. Cross-sectional study. This study included 146 participants: 47 younger adults (23 men and 24 women; age range 23-44 years) recruited from a dental hospital and 99 community-dwelling older adults (37 men and 62 women, age range 65-86 years). Age (<65 years or ≥65 years), body mass index (BMI), skeletal muscle mass index (SMI), and tooth loss (Eichner classification) were measured. The cross-sectional areas (CSAs) of the tongue, geniohyoid muscle, and anterior belly of the digastric muscle were measured using an ultrasonic diagnostic apparatus. The correlation between each muscle's CSA and strength was examined. Multiple regression analyses were performed separately for each sex using each muscle CSA as the dependent variable and age, BMI, SMI, and the Eichner classification as explanatory variables. Older men had a significant positive correlation between tongue pressure and CSA (r = 0.35, P = .031). Jaw opening force was positively correlated with geniohyoid muscle CSA (r = 0.41, P = .001) in older women. In the multiple regression analysis, age, BMI, and SMI were significantly associated with tongue CSA in men. Age was significantly and inversely associated with suprahyoid muscle CSA in both men and women. No explanatory variables were significantly associated with geniohyoid muscle CSA except age. The tongue increased in volume, and the suprahyoid muscles underwent atrophy with age. The study results suggest that interventions to prevent dysphagia associated with aging should be tailored toward specific muscles. Direct muscle training is required for the suprahyoid muscles, whereas the maintenance of tongue muscle mass and function, as well as training for the tongue, requires attention to ensure optimal nutritional status and whole-body skeletal muscle mass.

MeSH Terms

-

Keywords

Aging; body mass index; cross-sectional area; digastric muscle; geniohyoid muscle; tongue

Development of a Geropathology Grading Platform for nonhuman primates.

Abstract

A geropathology grading platform (GGP) for assessing age-related lesions has been established and validated for in inbred strain of mice. Because nonhuman primates (NHPs) share significant similarities in aging and spontaneous chronic diseases with humans, they provide excellent translational value for correlating histopathology with biological and pathological events associated with increasing age. Descriptive age-associated pathology has been described for rhesus macaques and marmosets, but a grading platform similar to the mouse GGP does not exist. The value of these NHP models is enhanced by considerable historical data from clinical, bio-behavioral, and social domains that align with health span in these animals. Successful adaptation of the mouse GGP for NHPs will include 1) expanding the range of organs examined; 2) standardizing necropsy collection, tissue trimming, and descriptive lesion terminology; 3) expanding beyond rhesus macaques and marmosets to include other commonly used NHPs in research; and 4) creating a national resource for age-related pathology to complement the extensive in-life datasets. Adaptation of the GGP to include translational models other than mice will be crucial to advance geropathology designed to enhance aging research.

MeSH Terms

-

Keywords

Aging; age-related diseases; geropathology; geroscience; marmosets; mice; nonhuman primates; rhesus macaques

Age-Related Frailty: A Clinical Model for Geroscience?

Abstract

In their everyday practice, geriatricians are confronted with the fact that older age and multimorbidity are associated to frailty. Indeed, if we take the example of a very old person with no diseases that progressively becomes frail with no other explanation, there is a natural temptation to link frailty to aging. On the other hand, when an old person with a medical history of diabetes, arthritis and congestive heart failure becomes frail there appears an obvious relationship between frailty and comorbidity. The unsolved question is: Considering that frailty is multifactorial and in the majority of cases comorbidity and aging are acting synergistically, can we disentangle the main contributor to the origin of frailty: disease or aging? We believe that it is important to be able to differentiate age-related frailty from frailty related to comorbidity. In fact, with the emergence of geroscience, the physiopathology, diagnosis, prognosis and treatment will probably have to be different in the future.

MeSH Terms

-

Keywords

Frailty causes; age-related frailty; aging; frailty related to diseases; geroscience

Age-Dependent Decline in Synaptic Mitochondrial Function Is Exacerbated in Vulnerable Brain Regions of Female 3xTg-AD Mice.

Abstract

Synaptic aging has been associated with neuronal circuit dysfunction and cognitive decline. Reduced mitochondrial function may be an early event that compromises synaptic integrity and neurotransmission in vulnerable brain regions during physiological and pathological aging. Thus, we aimed to measure mitochondrial function in synapses from three brain regions at two different ages in the 3xTg-AD mouse model and in wild mice. We found that aging is the main factor associated with the decline in synaptic mitochondrial function, particularly in synapses isolated from the cerebellum. Accumulation of toxic compounds, such as tau and Aβ, that occurred in the 3xTg-AD mouse model seemed to participate in the worsening of this decline in the hippocampus. The changes in synaptic bioenergetics were also associated with increased activation of the mitochondrial fission protein Drp1. These results suggest the presence of altered mechanisms of synaptic mitochondrial dynamics and their quality control during aging and in the 3xTg-AD mouse model; they also point to bioenergetic restoration as a useful therapeutic strategy to preserve synaptic function during aging and at the early stages of Alzheimer's disease (AD).

MeSH Terms

-

Keywords

amyloid-β protein; brain aging; mitochondrial dynamics; synaptic mitochondria; synaptosomes; tau

Serine and Metabolism Regulation: A Novel Mechanism in Antitumor Immunity and Senescence.

Abstract

As one of the nonessential amino acids (NEAAs), serine is involved in the anabolism of multiple macromolecular substances by participating in one-carbon unit metabolism. Thus, rapidly proliferating cells such as tumor cells and activated immune cells are highly dependent on serine. Serine supports the proliferation of various immune cells through multiple pathways to enhance the antitumor immune response. Moreover, serine influences aging specificity in an epigenetic and metabolic manner. In this review, we focus on recent advances in the relationship between serine metabolism, antitumor immunity, and senescence. The metabolic regulation of serine seems to be a key point of intervention in antitumor immunity and aging-related disease, providing an opportunity for several novel therapeutics.

MeSH Terms

-

Keywords

Serine; antitumor immunity and senescence; metabolism

Receptor tyrosine kinases-instructed release of its inhibitor from hydrogel to delay ovarian aging.

Abstract

Premature ovarian failure (POF) is the most frequently occurred disease in ovary. Direct inhibition of mammalian target of rapamycin (mTOR) activity can treat woman POF but brings adverse effects to women. Herein, by rational design of a hydrogelator Nap-Phe-Phe-Asp-Arg-Leu-Tyr-OH (Y) and co-assembling Y with an inhibitor of receptor tyrosine kinase (RTK, an upstream kinase of mTOR), Ala-Glu-Ala-Ala-Leu-Tyr-Lys-Asn-Leu-Leu-His-Ser-OH (Inh), to form hydrogel Gel Y + Inh, we develop a "smart" strategy of RTK-responsive disassembly of the hydrogel to release Inh. Release of Inh moderately inhibits the activity of mTOR and therefore delays ovarian aging. Oocyte and zygote experiments show that Gel Y + Inh improves both meiotic maturation of the oocytes and early embryonic development of the zygotes. In vivo animal experiments indicate that Gel Y + Inh effectively delays ovarian aging in aged mice by down regulation of mTOR activity, stimulation of ovaries to secrete estrogen and progesterone, and development of more antral follicles for reproduction. We expect that our new hydrogel Gel Y + Inh could be applied to treat woman POF, as well as delay ovarian aging, in clinic in the near future.

MeSH Terms

-

Keywords

Hydrogel; Ovarian aging; Receptor tyrosine kinases; Responsive release

Taurine Attenuates Catabolic Processes Related to the Onset of Sarcopenia.

Abstract

Sarcopenia that occurs with advancing age is characterized by a gradual loss of muscle protein component due to the activation of catabolic pathways, increased level of inflammation, and mitochondrial dysfunction. Experimental evidence demonstrates that several physio-pathological processes involved in the onset of sarcopenia may be counteracted by the intake of specific amino acids or antioxidant molecules, suggesting that diet may represent an effective strategy for improving the anabolic response of muscle during aging. The non-essential amino acid taurine is highly expressed in several mammalian tissues, including skeletal muscle where it is involved in the ion channel regulation, in the modulation of intracellular calcium concentration, and where it plays an important role as an antioxidant and anti-inflammatory factor. Here, with the purpose to reproduce the chronic low-grade inflammation characteristics of senescent muscle in an in vitro system, we exploited the role of Tumor Necrosis Factor α (TNF) and we analyzed the effect of taurine in the modulation of different signaling pathways known to be dysregulated in sarcopenia. We demonstrated that the administration of high levels of taurine in myogenic L6 cells stimulates the differentiation process by downregulating the expression of molecules involved in inflammatory pathways and modulating processes such as autophagy and apoptosis. Although further studies are currently ongoing in our laboratory to better elucidate the molecular mechanisms responsible for the positive effect of taurine on myogenic differentiation, this study suggests that taurine supplementation may represent a strategy to delay the loss of mass and functionality characteristic of senescent muscles.

MeSH Terms

-

Keywords

aging; antioxidants; autophagy; inflammation; nutrition; skeletal muscle

Late Passage Cultivation Induces Aged Astrocyte Phenotypes in Rat Primary Cultured Cells.

Abstract

Astrocytes play various important roles such as maintaining brain homeostasis, supporting neurons, and secreting inflammatory mediators to protect the brain cells. In aged subjects, astrocytes show diversely changed phenotypes and dysfunctions. But, the study of aged astrocytes or astrocytes from aged subjects is not yet sufficient to provide a comprehensive understanding of their important processes in the regulation of brain function. In this study, we induced an [i]in vitro[/i] aged astrocyte model through late passage cultivation of rat primary cultured astrocytes. Astrocytes were cultured until passage 7 (P7) as late passage astrocytes and compared with passage 1 (P1) astrocytes as early passage astrocytes to confirm the differences in phenotypes and the effects of serial passage. In this study, we confirmed the morphological, molecular, and functional changes of late passage astrocytes showing aging phenotypes through SA-β-gal staining and measurement of nuclear size. We also observed a reduced expression of inflammatory mediators including IL-1β, IL-6, TNFα, iNOS, and COX2, as well as dysregulation of wound-healing, phagocytosis, and mitochondrial functions such as mitochondrial membrane potential and mitochondrial oxygen consumption rate. Cultureconditioned media obtained from P1 astrocytes promoted neurite outgrowth in immature primary cultures of rat cortices, which is significantly reduced when we treated the immature neurons with the culture media obtained from P7 astrocytes. These results suggest that late passage astrocytes show senescent astrocyte phenotypes with functional defects, which makes it a suitable model for the study of the role of astrocyte senescence on the modulation of normal and pathological brain aging.

MeSH Terms

-

Keywords

Astrocytes; Cellular senescence; Late passage cultivation; Neuro-inflammatory response; Phagocytosis; Wound healing

Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats.

Abstract

Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models. In vitro, cyanidin-3-rutinoside (C-3-R) and cyanidin-3-glucoside (C-3-G) inhibited the d-galactose (d-gal)-induced senescence in human endothelial cells, as indicated by reduced senescence-associated-β-galactosidase activity, p21, and p16 . Anthocyanins blocked d-gal-induced reactive oxygen species (ROS) formation and NADPH oxidase activity. Anthocyanins reversed d-gal-mediated inhibition of endothelial nitric oxide synthase (eNOS) serine phosphorylation and SIRT1 expression, recovering NO level in endothelial cells. Also, SIRT1-mediated eNOS deacetylation was shown to be involved in anthocyanin-enhanced eNOS activity. In vivo, anthocyanin-rich mulberry extract was administered to aging rats for 8 weeks. In vivo, mulberry extract alleviated endothelial senescence and oxidative stress in the aorta of aging rats. Consistently, mulberry extract also raised serum NO levels, increased phosphorylation of eNOS, increased SIRT1 expression, and reduced nitrotyrosine in aortas. The eNOS acetylation was higher in the aging group and was restored by mulberry extract treatment. Similarly, SIRT1 level associated with eNOS decreased in the aging group and was restored in aging plus mulberry group. These findings indicate that anthocyanins protect against endothelial senescence through enhanced NO bioavailability by regulating ROS formation and reducing eNOS uncoupling.

MeSH Terms

-

Keywords

NO; SIRT1; anthocyanins; eNOS deacetylation; senescence

Eating Problems in Advanced Dementia: Navigating Difficult Conversations.

Abstract

The majority of older adults with advanced dementia (AD) develop difficulties with eating and swallowing, often prompting concerns about nutrition and quality of life. Employing a palliative approach requires providers to attain skills in addressing symptoms and communicating with family caregivers about the trajectory of AD and associated dysphagia, as well as to elicit goals of care. Research suggests internal medicine (IM) residents often perceive minimal education during training addressing skills needed to care for patients with AD. We developed and piloted a small-group interactive seminar utilizing a trigger video depicting a family meeting addressing eating problems in a patient with AD. Case-based learning, small-group discussion, and learner reflection were employed. We assessed the impact on 82 of the 106 IM, medicine-pediatrics, and neurology residents who participated in the seminar. Participant evaluation indicated residents showed high satisfaction and perceived the educational content of the seminar to be robust and clinically relevant. We found statistically significant ([i]p[/i] < .001) improvements in self-reported confidence in dementia-specific skills postseminar. Effect size was large to very large (Cohen's [i]d[/i] = 1.3-1.7). An interactive, case-based seminar utilizing a video depicting a realistic family meeting improved residents' self-efficacy in skills needed to address nutritional issues, engage in goals-of-care discussions, and reflect on concerns among caregivers of patients with AD. The seminar teaches important geriatric and palliative concepts meant to improve residents' ability to care for older adults with AD in their future careers.

MeSH Terms

-

Keywords

Advanced Dementia; Case-Based Learning; Dysphagia; Geriatrics; Geriatrics Education; Hospice & Palliative Medicine; Palliative Care Education; Resident Education

Long-term intake of the illegal diet pill DNP reduces lifespan in a captive bird model.

Abstract

2,4-Dinitrophenol (DNP), a molecule uncoupling mitochondrial oxidative phosphorylation from oxygen consumption, is illegally used by humans as a diet pill, but is nonetheless investigated as a potential human medicine against 'metabesity'. Due to its proven acute toxicity and the scarceness of long-term studies on DNP administration in vertebrates, we determined the impact of a long-term DNP treatment (~4 mg.kg .day , i.e. within the range taken illegally by humans) on body mass, metabolism, ageing and lifespan in a captive bird model, the zebra finch. The chronic absorption of DNP over life (>4 years) led to a mild increase in energy expenditure (ca. +11% compared to control group), without significantly altering the normal slight increase in body mass with age. DNP did not significantly influence the alteration of physical performance, the rise in oxidative damage, or the progressive shortening of telomeres with age. However, DNP-treated individuals had a significantly shorter lifespan (ca. -21% in median lifespan compared to control group), thereby raising potential concerns about DNP use as a diet pill or medicine.

MeSH Terms

-

Keywords

2,4-Dinitrophenol; Longevity; Mitochondrial uncoupling; Oxidative stress; Survival; Toxicity

Nutrients and Pathways that Regulate Health Span and Life Span.

Abstract

Both life span and health span are influenced by genetic, environmental and lifestyle factors. With the genetic influence on human life span estimated to be about 20-25%, epigenetic changes play an important role in modulating individual health status and aging. Thus, a main part of life expectance and healthy aging is determined by dietary habits and nutritional factors. Excessive or restricted food consumption have direct effects on health status. Moreover, some dietary interventions including a reduced intake of dietary calories without malnutrition, or a restriction of specific dietary component may promote health benefits and decrease the incidence of aging-related comorbidities, thus representing intriguing potential approaches to improve healthy aging. However, the relationship between nutrition, health and aging is still not fully understood as well as the mechanisms by which nutrients and nutritional status may affect health span and longevity in model organisms. The broad effect of different nutritional conditions on health span and longevity occurs through multiple mechanisms that involve evolutionary conserved nutrient-sensing pathways in tissues and organs. These pathways interacting each other include the evolutionary conserved key regulators mammalian target of rapamycin, AMP-activated protein kinase, insulin/insulin-like growth factor 1 pathway and sirtuins. In this review we provide a summary of the main molecular mechanisms by which different nutritional conditions, i.e., specific nutrient abundance or restriction, may affect health span and life span.

MeSH Terms

-

Keywords

aging; health span; life span; nutrient-sensing pathways; nutrients

The bright and dark side of skin senescence. Could skin rejuvenation anti-senescence interventions become a "bright" new strategy for the prevention of age-related skin pathologies?

Abstract

The number of senescent cells in the skin is increasing with age. Numerous studies have attempted to elucidate the role of these cells in normal aging of the skin as well as in age-related skin conditions. In recent years, attempts have also been made to find treatments that aim either to cleanse the skin tissues of senescent cells or to neutralize their effects (referred to as senolytics and senomorphics respectively) and thus prevent the consequences, particularly on the skin's appearance in advanced age. Through this review, we have tried to gather data on the role of senescent cells in the skin, in treatments aimed at removing them, and we are asking a reasonable question as to whether anti-senescence treatments may contribute to the protection against age-related skin pathologies, including skin cancer, such as non-melanoma skin cancer, in addition to their involvement in skin rejuvenation.

MeSH Terms

-

Keywords

Cellular senescence; Senolytics; Skin aging

Age-related altering temporal processing and binaural interaction functions in normal hearing individuals: Observational and cross-sectional study.

Abstract

This study aimed to investigate the temporal processing and binaural interaction functions of central auditory processing tests according to the anatomical localizations of young and elderly individuals. It also sought to evaluate the relationships between the same individuals' central auditory processing tests. This observational and cross-sectional study included individuals with normal hearing between 18 and 30 and 60-75 years of age, who were referred to as the young group and the elderly group, respectively. The evaluation of the central auditory processing tests was completed using the frequency pattern test, duration pattern test, masking level difference test, and random gap detection test. Furthermore, speech discrimination and speech in noise scores were analyzed for both groups. Statistically significant differences were identified between the groups' scores for the speech in noise test, masking level difference test, random gap detection test, frequency pattern test, and duration pattern test (p < 0.05). A statistically significant relationship was observed between the age and the results of the central auditory processing tests (p < 0.05). When compared to younger individuals, elderly individuals presented with declined temporal sequences, temporal resolutions, and binaural interaction skills.

MeSH Terms

-

Keywords

Aging; Duration pattern; Elderly; Frequency pattern; Gap detection; Masking level difference

Oxidative Stress at the Crossroads of Aging, Stroke and Depression.

Abstract

Epidemiologic studies have shown that in the aging society, a person dies from stroke every 3 minutes and 42 seconds, and vast numbers of people experience depression around the globe. The high prevalence and disability rates of stroke and depression introduce enormous challenges to public health. Accumulating evidence reveals that stroke is tightly associated with depression, and both diseases are linked to oxidative stress (OS). This review summarizes the mechanisms of OS and OS-mediated pathological processes, such as inflammation, apoptosis, and the microbial-gut-brain axis in stroke and depression. Pathological changes can lead to neuronal cell death, neurological deficits, and brain injury through DNA damage and the oxidation of lipids and proteins, which exacerbate the development of these two disorders. Additionally, aging accelerates the progression of stroke and depression by overactive OS and reduced antioxidant defenses. This review also discusses the efficacy and safety of several antioxidants and antidepressants in stroke and depression. Herein, we propose a crosstalk between OS, aging, stroke, and depression, and provide potential therapeutic strategies for the treatment of stroke and depression.

MeSH Terms

-

Keywords

aging; antioxidant; depression; intracerebral hemorrhage; mitochondrial dysfunction; oxidative stress; stroke; subarachnoid hemorrhage

Adherence to Beers Criteria in Geriatrics: A Retrospective Study in a Saudi Teaching Hospital.

Abstract

The aging process makes geriatric populations more prone to various chronic diseases. Such diseases require older patients to be on more medications than any other age group and make them more susceptible to adverse drug events related to potentially inappropriate medications (PIMs). To identify the prevalence of potentially inappropriate medications among older people and explore the most commonly prescribed PIMs in hospitalized patients. A retrospective study conducted in a large tertiary hospital among patients hospitalized in a 4 year period from January 2015 to December 2018. The 2019 Beers Criteria were used to assess PIMs in all inpatient prescribed medications focusing on the first class (i.e., drug/drug class to be avoided in older adults). The mean age was 75.17 ± 7.66 years. A total of 684 (80.6%) patients were prescribed at least one medication listed in the first-class category of the 2019 Beers Criteria. Top five drugs were proton pump inhibitors (40.3%), nonsteroidal anti-inflammatory drugs (10.2%), metoclopramide (9.3%), benzodiazepines (8.4%), and insulin (5.4%). The prevalence of PIMs is high among older patients admitted to the hospital. More efforts are needed to investigate the potential reasons and develop action plans to improve concordance to Beers Criteria among healthcare providers.

MeSH Terms

-

Keywords

Beers criteria; adherence; geriatrics; potential inappropriate medications

Tyramine Acts Downstream of Neuronal XBP-1s to Coordinate Inter-tissue UPR Activation and Behavior in C. elegans.

Abstract

In C. elegans, expression of the UPR transcription factor xbp-1s in neurons cell non-autonomously activates the UPR in the intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated neurons from animals expressing neuronal xbp-1s for transcriptomic analysis, revealing a striking remodeling of transcripts involved in neuronal signaling. We then identified signaling molecules required for cell non-autonomous intestinal UPR activation, including the biogenic amine tyramine. Expression of xbp-1s in just two pairs of neurons that synthesize tyramine, the RIM and RIC interneurons, induced intestinal UPR activation and extended longevity, and exposure to stress led to splicing and activation of xbp-1 in these neurons. In addition, we found that neuronal xbp-1s modulates feeding behavior and reproduction, dependent upon tyramine synthesis. XBP-1s therefore remodels neuronal signaling to coordinately modulate intestinal physiology and stress-responsive behavior, functioning as a global regulator of organismal responses to stress.

MeSH Terms

-

Keywords

C. elegans; ER stress; aging; neurobiology; proteostasis; signaling; stress response

Age- and gender-associated differences in the sleepy brain's electroencephalogram.

Abstract

In eyes closed condition, an increase of sleepiness level is associated with a decrease of the spectral electroencephalographic (EEG) power in the fast frequency rage (i.e., alpha activity) and with an increase of the power in the slow frequency range (i.e., theta activity). It was suggested that the changes in the fast and slow frequency ranges might determine two - the earlier and later - drowsiness stages preceding sleep onset, respectively. We tested whether such spectral EEG signatures of sleepiness vary with age or gender. The EEG signal was recorded with two-h intervals in 48 volunteers (15-67 years, 27 females) deprived from sleep between Friday evening to Sunday evening. The EEG signatures of sleepiness were calculated by the expressing each EEG spectrum as a deviation from the initial (Friday evening) EEG spectrum. The age- and gender-specific variation in such signatures was found. Only the pattern of age-associated variation changed with an increase of sleepiness level. Two-stage response to the increase of sleepiness was confirmed, but only in younger study participants. Subjective sleepiness was associated with neither age nor gender. In sleep deprivation research, the accounting for the age- and gender-specific variation in the spectral EEG measures of drowsiness might be recommended. The results did not reveal any disturbance of motivational function of subjective sleepiness in older study participants.

MeSH Terms

-

Keywords

aging; alertness; alpha attenuation; alpha rhythm; drowsiness; gender; spectral EEG

Circular RNAs: Promising Biomarkers for Age-related Diseases.

Abstract

Aging is a complex biological process closely linked with the occurrence and development of age-related diseases. Despite recent advances in lifestyle management and drug therapy, the late diagnosis of these diseases causes severe complications, usually resulting in death and consequently impacting social economies. Therefore, the identification of reliable biomarkers and the creation of effective treatment alternatives for age-related diseases are needed. Circular RNAs (circRNAs) are a novel class of RNA molecules that form covalently closed loops capable of regulating gene expression at multiple levels. Several studies have reported the emerging functional roles of circRNAs in various conditions, providing new perspectives regarding cellular physiology and disease pathology. Notably, accumulating evidence demonstrates the involvement of circRNAs in the regulation of age-related pathologies, including cardio-cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis. Therefore, the association of circRNAs with these age-related pathologies highlights their potential as diagnostic biomarkers and therapeutic targets for better disease management. Here, we review the biogenesis and function of circRNAs, with a special focus on their regulatory roles in aging-related pathologies, as well as discuss their potential as biological biomarkers and therapeutic targets for these diseases.

MeSH Terms

-

Keywords

age-related diseases; aging; biomarker; circRNAs

PsychoAge and SubjAge: development of deep markers of psychological and subjective age using artificial intelligence.

Abstract

Aging clocks that accurately predict human age based on various biodata types are among the most important recent advances in biogerontology. Since 2016 multiple deep learning solutions have been created to interpret facial photos, omics data, and clinical blood parameters in the context of aging. Some of them have been patented to be used in commercial settings. However, psychological changes occurring throughout the human lifespan have been overlooked in the field of "deep aging clocks". In this paper, we present two deep learning predictors trained on social and behavioral data from Midlife in the United States (MIDUS) study: (a) PsychoAge, which predicts chronological age, and (b) SubjAge, which describes personal aging rate perception. Using 50 distinct features from the MIDUS dataset these models have achieved a mean absolute error of 6.7 years for chronological age and 7.3 years for subjective age. We also show that both PsychoAge and SubjAge are predictive of all-cause mortality risk, with SubjAge being a more significant risk factor. Both clocks contain actionable features that can be modified using social and behavioral interventions, which enables a variety of aging-related psychology experiment designs. The features used in these clocks are interpretable by human experts and may prove to be useful in shifting personal perception of aging towards a mindset that promotes productive and healthy behaviors.

MeSH Terms

-

Keywords

aging clock; artificial intelligence; deep learning; psychology of aging; subjective age

Are Loneliness and Social Isolation Associated with Quality of Life in Older Adults? Insights from Northern and Southern Europe.

Abstract

Loneliness and social isolation have detrimental effects on health in old age; however, the prospective associations with quality of life (QoL) remain unclear. Furthermore, despite the existence of a European north-south gradient in the distribution of loneliness and social isolation, little is known whether the associations are context-specific. We investigated the relationships between loneliness, social isolation and QoL of older adults residing in the North (Sweden) and South (Spain) of Europe. Study sample consisted of 2995 Swedish and 4154 Spanish older adults who participated in waves six and seven of the Study on Health, Aging and Retirement in Europe (SHARE). Loneliness and social isolation were measured at the baseline, and QoL was measured at the baseline and follow-up using CASP-12. Prospective associations were assessed via multivariate linear regression. In Sweden, subjects with higher vs. lower loneliness had 1.01 (95% CI: -1.55, -0.40) units lower QoL, while every standard deviation increase in social isolation was associated with a 0.27 (95% CI: -0.42, -0.09)-unit decrease in QoL. In Spain, every standard deviation increase in social isolation was associated with a 0.66 (95% CI: -1.11, -0.22)-unit decrease in QoL. The association was stronger in subjects aged ≤65 years old and those with no chronic diseases. The association with loneliness was not statistically significant in Spain. Loneliness and social isolation are prospectively associated with decreased QoL among older adults, yet the associations are contextually bound. Future interventions should target both exposures, among others, in order to increase QoL in this group.

MeSH Terms

-

Keywords

SHARE; aging; loneliness; prospective studies; quality of life; social isolation

Accelerating bone healing in vivo by harnessing the age-altered activation of c-Jun N-terminal kinase 3.

Abstract

We have recently demonstrated that c-Jun N-terminal kinase 3 (JNK3) is a key modulator of the enhanced osteogenic potential of stem cells derived from children when compared to those derived from adults. In this study, we formulated a JNK3-activator nanoparticle (JNK3*) that recapitulates the immense osteogenic potential of juvenile cells in adult stem cells by facilitating JNK3 activation. Moreover, we aimed to functionalize a collagen-based scaffold by incorporating the JNK3* in order to develop an advanced platform capable of accelerating bone healing by recruitment of host stem cells. Our data, in vitro and in vivo, demonstrated that the immense osteogenic potential of juvenile cells could be recapitulated in adult stem cells by facilitating JNK3 activation. Moreover, our results revealed that the JNK3* functionalized 3D scaffold induced the fastest bone healing and greatest blood vessel infiltration when implanted in critical-size rat calvarial defects in vivo. JNK3*scaffold fastest bone healing in vivo was associated with its capacity to recruit host stem cells to the site of injury and promote angiogenic-osteogenic coupling (e.g. Vegfa, Tie1, Runx2, Alp and Igf2 upregulation). In summary, this study has demonstrated the potential of harnessing knowledge of age-altered stem cell mechanobiology in order to develop a materials-based functionalization approach for the repair of large tissue defects.

MeSH Terms

-

Keywords

Aging; Bone healing; Mechanobiology; Scaffold; Therapeutic; jnk3

The Effects of Low-Intensity Multimodal Proprioceptive Exercise on Cognitive Function in Older Adults.

Abstract

Physical activity provides a number of physical and psychological benefits. Multimodal proprioceptive exercise represents a useful balance-based exercise with the potential to reduce falls in older adults. Previous research has also indicated cognitive benefits following multimodal proprioceptive exercise in young and older adults. This study aimed to assess cognition and mood following 2 types of physical activity (multimodal proprioception vs yoga) compared with control (classroom-based) in healthy older adults. Nineteen older adults (Mage = 65, sex = 9 males) participated in this randomized controlled crossover trial. Participants completed a 20-minute multimodal proprioceptive exercise class, 20-minute yoga session, and 20-minute classroom-based control. Numeric working memory and mood were assessed before and immediately following each of the interventions. The multimodal proprioceptive intervention significantly reduced numeric working memory reaction time versus the yoga (P = .043) and control (P = .023) group. There were no differences found for accuracy or mood. These results indicate that multimodal proprioceptive exercise is worthy of further investigation as an alternative mode of exercise alongside the more traditional aerobic and strength-based exercise for healthy older adults.

MeSH Terms

-

Keywords

aging; cognition; mood; proprioception

Peripheral visual perception during natural overground dual-task walking in older and younger adults.

Abstract

Little is known about the neurophysiological processes underlying visual processing during active behavior and how these change over the life span. This study investigated early (P1) and later (P3) event-related potentials of the electroencephalogram associated with visual perception in older and younger adults while sitting, standing, and walking. While sitting and standing, accurate performance in both groups was not associated with event-related potential characteristics. During walking, in contrast, prolonged latencies and reduced amplitudes of the P1 were related to slower responses and increased misses, respectively. No covariations of behavior and P3 characteristics were observed. However, prolonged P3 latencies with increasing motor task complexity were present for both age groups, and reduced amplitudes while walking were replicated in younger participants. Older participants were more affected by walking in general as reflected in slower walking speeds as well as reduced accuracy and relative P1 amplitudes. These results provide further insights into cognitive-motor interference during natural walking in younger and older adults on early attentional-perceptual processing stages, even for simple additional visual tasks.

MeSH Terms

-

Keywords

Aging; Dual-task walking; EEG; MoBI; Peripheral visual perception

Effects of [i]Cudrania tricuspidata[/i] on anti-senescence in high glucose-treated endothelial cells via the Akt/p53/p21 pathway.

Abstract

The roles of [i]Cudrania tricuspidata[/i] (CT) in the prevention of senescence and the underlying mechanisms have not been elucidated. In a high glucose (HG)-induced senescent endothelial cell (EC) culture, CT (20 µg/ml) reduced the number of senescence-associated β-galactosidase-positive cells by 8.3% compared with the control group and increased the expression of p-Sirt1 by more than twofold compared with the control group. Moreover, 20 μg/ml CT treatment doubled the activity of p-Akt, which was inhibited by HG, compared with the control group. In addition, CT treatment decreased the expression of p53, p21, and Rb, which was increased by HG. Overall, CT delays HG-induced senescence via the Akt/p53/p21 pathway, suggesting its potential as a functional agent for the protection of ECs.

MeSH Terms

-

Keywords

Akt/p53/p21; Cudrania tricuspidata; endothelial cell; senescence

A case report of traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) in a 21-year-old.

Abstract

We present an unusual case of a persistent solitary left palatoglossal ulcer with no history of trauma or associated risk factors. A TUGSE lesion, which mimics that of malignancy, must always be noted as a differential even in risk factor absence.

MeSH Terms

-

Keywords

TUGSE; Ulceration; carcinoma; dentistry; geriatrics; maxillofacial

Differential Brain Activity in Regions Linked to Visuospatial Processing During Landmark-Based Navigation in Young and Healthy Older Adults.

Abstract

Older adults have difficulties in navigating unfamiliar environments and updating their wayfinding behavior when faced with blocked routes. This decline in navigational capabilities has traditionally been ascribed to memory impairments and dysexecutive function, whereas the impact of visual aging has often been overlooked. The ability to perceive visuospatial information such as salient landmarks is essential to navigating efficiently. To date, the functional and neurobiological factors underpinning landmark processing in aging remain insufficiently characterized. To address this issue, functional magnetic resonance imaging (fMRI) was used to investigate the brain activity associated with landmark-based navigation in young and healthy older participants. The performances of 25 young adults (μ = 25.4 years, [i]σ[/i] = 2.7; seven females) and 17 older adults (μ = 73.0 years, [i]σ[/i] = 3.9; 10 females) were assessed in a virtual-navigation task in which they had to orient using salient landmarks. The underlying whole-brain patterns of activity as well as the functional roles of specific cerebral regions involved in landmark processing, namely the parahippocampal place area (PPA), the occipital place area (OPA), and the retrosplenial cortex (RSC), were analyzed. Older adults' navigational abilities were overall diminished compared to young adults. Also, the two age groups relied on distinct navigational strategies to solve the task. Better performances during landmark-based navigation were associated with increased neural activity in an extended neural network comprising several cortical and cerebellar regions. Direct comparisons between age groups revealed that young participants had greater anterior temporal activity. Also, only young adults showed significant activity in occipital areas corresponding to the cortical projection of the central visual field during landmark-based navigation. The region-of-interest analysis revealed an increased OPA activation in older adult participants during the landmark condition. There were no significant between-group differences in PPA and RSC activations. These preliminary results hint at the possibility that aging diminishes fine-grained information processing in occipital and temporal regions, thus hindering the capacity to use landmarks adequately for navigation. Keeping sight of its exploratory nature, this work helps towards a better comprehension of the neural dynamics subtending landmark-based navigation and it provides new insights on the impact of age-related visuospatial processing differences on navigation capabilities.

MeSH Terms

-

Keywords

fMRI; healthy aging; landmark; scene-selective regions; spatial navigation

Human Brain Ages With Hierarchy-Selective Attenuation of Prediction Errors.

Abstract

From the perspective of predictive coding, our brain embodies a hierarchical generative model to realize perception, which proactively predicts the statistical structure of sensory inputs. How are these predictive processes modified as we age? Recent research suggested that aging leads to decreased weighting of sensory inputs and increased reliance on predictions. Here we investigated whether this age-related shift from sensorium to predictions occurs at all levels of hierarchical message passing. We recorded the electroencephalography responses with an auditory local-global paradigm in a cohort of 108 healthy participants from 3 groups: seniors, adults, and adolescents. The detection of local deviancy seems largely preserved in older individuals at earlier latency (including the mismatch negativity followed by the P3a but not the reorienting negativity). In contrast, the detection of global deviancy is clearly compromised in older individuals, as they showed worse task performance and attenuated P3b. Our findings demonstrate that older brains show little decline in sensory (i.e., first-order) prediction errors but significant diminution in contextual (i.e., second-order) prediction errors. Age-related deficient maintenance of auditory information in working memory might affect whether and how lower-level prediction errors propagate to the higher level.

MeSH Terms

-

Keywords

aging; auditory perception; electroencephalography (EEG); prediction errors; predictive coding

A matter of time: Circadian clocks in osteoarthritis and the potential of chronotherapy.

Abstract

Osteoarthritis (OA) is a common and debilitating joint disease which develops and progresses with age. Despite extensive research into the disease, potent disease-modifying drugs remain elusive. Changes to the character and function of chondrocytes of the articular cartilage underly the pathogenesis of OA. A recently emerging facet of chondrocyte biology that has been implicated in OA pathogenesis is the role of circadian rhythms, and the cellular clock which governs rhythmic gene transcription. Here, we review the role of the chondrocyte's cellular clock in governing normal homeostasis, and explore the wide range of consequences that contribute to OA development when the clock is dysregulated by aging and other factors. Finally, we explore how harnessing this understanding of clock mechanics in aging and OA can be translated into novel treatment strategies, or 'chronotherapies', for patients.

MeSH Terms

-

Keywords

Aging; Chondrocyte; Circadian rhythms; Osteoarthritis; Translation

Age-related impairment of autophagy in cervical motor neurons.

Abstract

Neuromuscular dysfunction is common in old age. Damaged cytoplasmic structures aggregate with aging, especially in post-mitotic cells like motor neurons. Autophagy is a ubiquitous cell process that aids in the clearance of damaged aggregates. Accordingly, we hypothesized that autophagy is impaired in old age, contributing to neuromuscular dysfunction via an effect in motor neurons. Autophagy flux may be impaired as a result of deficits in the initiation, elongation or degradation phases. Changes in the expression levels of core proteins necessary for each of the autophagy phases were evaluated by Western blotting in the cervical spinal cord (segments C2-C6 corresponding to the phrenic motor pool) of adult male and female mice at 6-, 18-, and 24-months of age (reflecting 100%, 90% and 75% survival, respectively). There was no evidence of an effect of age on the expression of the autophagy markers Beclin-1 (Becn-1; initiation), ATG7 and ATG5/12 complex (elongation) or LC3 (elongation/degradation). Reduced p62 expression (a marker of degradation) was evident in the cervical spinal cord of adult mice at 18-months compared to 24-months. Accordingly, expression of LC3 and p62 in motor neurons was analyzed using immunofluorescence and confocal microscopy in separate animals. LC3 and p62 immunoreactivity was evident in the gray matter with minimal expression in the white matter across all age groups. A mixed linear model with animal as a random effect was used to compare relative LC3 and p62 expression in motor neurons to gray matter across age groups. Expression of both LC3 and p62 was higher in choline acetyl transferase (ChAT)-positive motor neurons (~2-3 fold vs. gray matter). Across age groups, there were differences in the relative expression of LC3 (F  = 7.59, p < 0.01) and p62 (F  = 8.00, p < 0.01) in cervical motor neurons. LC3 expression in motor neurons increased ~20% by 24-months of age in both male and female mice. p62 expression in motor neurons increased ~70% by 18-months compared to 6-months with no further changes by 24-months of age in male mice. p62 expression did not change across age groups in female mice, and was ~20% higher than in males. Our findings highlight important changes in autophagy pathways that likely contribute to the development of aging-related neuromuscular dysfunction in mice. At 18-months of age, increased autophagosome clearance (reduced p62 expression) appears to be a global effect not restricted to motor neurons. By 24-months of age, increased expression of LC3 and p62 indicates impaired autophagy with autophagosome accumulation in cervical motor neurons.

MeSH Terms

-

Keywords

Aging; Autophagy; Motor neuron; Neuromuscular dysfunction; Spinal cord

A novel digital clock drawing test as a screening tool for perioperative neurocognitive disorders: A feasibility study.

Abstract

We developed a digital clock drawing test (dCDT), an adaptation of the original pen and paper clock test, that may be advantageous over previous dCDTs in the perioperative environment. We trialled our dCDT on a tablet device in the preoperative period to determine the feasibility of administration in this setting. To assess the clinical utility of this test, we examined the relationship between the performance on the test and compared derived digital clock measures with the 4 A's Test (4AT), a delirium and cognition screening tool. We recruited a sample of 102 adults aged 65 years and over presenting for elective surgery in a single tertiary hospital. Participants completed the 4AT, followed by both command and copy clock conditions of the dCDT. We recorded time-based clock-drawing metrics, alongside clock replications scored using the Montreal Cognitive Assessment (MoCA) clock scoring criteria. The dCDT had an acceptance rate of 99%. After controlling for demographic variables and prior tablet use, regression analyses showed higher 4AT scores were associated with greater dCDT time (seconds) for both command (β=8.2, p=0.020) and copy clocks (β=12, p=0.005) and lower MoCA-based clock scores in both command (OR=0.19, p=0.001) and copy conditions (OR=0.14, p=0.012). The digital clock drawing test is feasible to administer and is highly acceptable to older adults in a preoperative setting. We demonstrated a significant association between both the dCDT time and clock score metrics, with the established 4AT. Our results provide convergent validity of the dCDT in the preoperative setting.

MeSH Terms

-

Keywords

aging; cognition; cognitive screening; feasibility; perioperative neurocognitive disorder

Aging and the encoding of changes in events: The role of neural activity pattern reinstatement.

Abstract

When encountering unexpected event changes, memories of relevant past experiences must be updated to form new representations. Current models of memory updating propose that people must first generate memory-based predictions to detect and register that features of the environment have changed, then encode the new event features and integrate them with relevant memories of past experiences to form configural memory representations. Each of these steps may be impaired in older adults. Using functional MRI, we investigated these mechanisms in healthy young and older adults. In the scanner, participants first watched a movie depicting everyday activities in a day of an actor's life. They next watched a second nearly identical movie in which some scenes ended differently. Crucially, before watching the last part of each activity, the second movie stopped, and participants were asked to mentally replay how the activity previously ended. Three days later, participants were asked to recall the activities. Neural activity pattern reinstatement in medial temporal lobe (MTL) during the replay phase of the second movie was associated with detecting changes and with better memory for the original activity features. Reinstatements in posterior medial cortex (PMC) additionally predicted better memory for changed features. Compared to young adults, older adults showed a reduced ability to detect and remember changes and weaker associations between reinstatement and memory performance. These findings suggest that PMC and MTL contribute to change processing by reinstating previous event features, and that older adults are less able to use reinstatement to update memory for changed features.

MeSH Terms

-

Keywords

change comprehension; cognitive aging; episodic memory; event cognition; representational similarity analysis

Conditional reprograming culture conditions facilitate growth of lower grade glioma models.

Abstract

The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture with irradiated fibroblasts and the addition of a small molecule Rho kinase (ROCK) inhibitor. The aim of this study was to determine whether this approach would facilitate the culture of compact low grade gliomas. We attempted to culture 4 pilocytic astrocytomas, 2 gangliogliomas, 2 myxopapillary ependymomas, 2 anaplastic gliomas, 2 difficult-to-classify low grade neuroepithelial tumors, a desmoplastic infantile ganglioglioma, and an anaplastic pleomorphic xanthoastrocytoma using a modified conditional reprogramming cell culture approach. Conditional reprogramming resulted in robust increases in growth for a majority of these tumors, with fibroblast conditioned media and ROCK inhibition both required. Switching cultures to standard serum containing media, or serum free neurosphere conditions, with or without ROCK inhibition, resulted in decreased proliferation and induction of senescence markers. ROCK inhibition and conditioned media both promoted Akt and Erk1/2 activation. Several cultures, including one derived from a NF1-associated pilocytic astrocytoma (JHH-NF1-PA1) and one from a BRAF p.V600E mutant anaplastic pleomorphic xanthoastrocytoma (JHH-PXA1), exhibited growth sufficient for preclinical testing in vitro. In addition, JHH-NF1-PA1 cells survived and migrated in larval zebrafish orthotopic xenografts, while JHH-PXA1 formed orthotopic xenografts in mice histopathologically similar to the tumor from which it was derived. These studies highlight the potential for the conditional reprogramming cell culture method to promote the growth of glial and glioneuronal tumors in vitro, in some cases enabling the establishment of long-term culture and in vivo models.

MeSH Terms

-

Keywords

BRAFV600E; Conditional reprogramming; NF1; Senescence; low grade glioma

The Functional Foundations of Episodic Memory Remain Stable Throughout the Lifespan.

Abstract

It has been suggested that specific forms of cognition in older age rely largely on late-life specific mechanisms. Here instead, we tested using task-fMRI (n = 540, age 6-82 years) whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural, and evolutionary influences. We clustered regions of the cerebral cortex according to the shape of the lifespan trajectory of memory activity in each region so that regions showing the same pattern were clustered together. The results revealed that lifespan trajectories of memory encoding function showed a continuity through life but no evidence of age-specific mechanisms such as compensatory patterns. Encoding activity was related to general cognitive abilities and variations of grey matter as captured by a multi-modal independent component analysis, variables reflecting core aspects of cognitive and structural change throughout the lifespan. Furthermore, memory encoding activity aligned to fundamental aspects of brain organization, such as large-scale connectivity and evolutionary cortical expansion gradients. Altogether, we provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only.

MeSH Terms

-

Keywords

aging; development; encoding; fMRI; neuroimaging

SIRT1 - a new mammalian substrate of nuclear autophagy.

Abstract

Macroautophagic/autophagic degradation of nuclear components (or nuclear autophagy) is a poorly understood area in autophagy research. We previously reported the nuclear lamina protein LMNB1 (lamin B1) as a nuclear autophagy substrate in primary human cells, stimulating the investigation of nuclear autophagy in the mammalian system. We recently reported the sirtuin protein SIRT1 as a new selective substrate of nuclear autophagy in senescence and aging. Upon senescence of primary human cells, SIRT1 degradation is mediated by a direct nuclear SIRT1-LC3 interaction, followed by nucleus-to-cytoplasm shuttling of SIRT1 and autophagosome-lysosome degradation. In vivo, SIRT1 is downregulated by lysosomes in hematopoietic and immune organs upon natural aging in mice and in aged human T cells. Our study identified another substrate of nuclear autophagy and suggests a new strategy to promote SIRT1-mediated health benefits by suppressing its autophagic degradation.

MeSH Terms

-

Keywords

Aging; SIRT1; nuclear autophagy; senescence; sirtuin

Circulating cell-free DNA species affect the risk of hepatocellular carcinoma in treated chronic hepatitis B patients.

Abstract

Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients even under effective long-term oral antiviral therapy, but its pathogenesis in the setting of long-standing inhibition of viral replication has not been completely elucidated. We investigated whether species of circulating cell-free DNA (cfDNA) may be involved in the process of hepatocarcinogenesis in treated CHB patients. Serum samples were obtained from HBeAg-negative CHB patients with (HCC cases, n=37) or without HCC development during the first 5 years of oral antiviral therapy (controls, n=74). HCC cases and controls were matched 1:2 for age, sex and platelets. Determination of different circulating cfDNA species (before HCC diagnosis in HCC cases) including total cfDNA quantity, levels of Alu repeat DNA and RNAse P coding DNA, copies of mitochondrial DNA and levels of 5-methyl-2'-deoxycytidine as indicator of DNA methylation was performed. HCC cases compared to controls had higher median levels of Alu247 (123 vs 69 genomic equivalent, P=0.042) and RNAse P coding DNA (68 vs 15 genomic equivalent, P<0.001). In contrast, median cfDNA concentration, Alu115 levels, Alu247/Alu115 ratio as an index of DNA integrity and mitochondrial DNA copies did not differ significantly between HCC cases and controls. Receiver operating characteristic curve analysis showed that levels RNAse P coding DNA offered good prediction of subsequent HCC development (c-statistic: 0.80, P<0.001). In conclusion, serum levels of RNAse P coding DNA are increased years before HCC diagnosis and could be potentially helpful in the prediction of the HCC risk in treated HBeAg-negative CHB patients.

MeSH Terms

-

Keywords

cirrhosis; hepatitis B; liver cancer; senescence; therapy

Inhibition of PAR-1 delays aging via activating AMPK in C. elegans.

Abstract

The antagonistic pleiotropy theory of aging suggests that genes essential for growth and development are likely to modulate aging later in life. Previous studies in [i]C. elegans[/i] demonstrate that inhibition of certain developmentally essential genes during adulthood leads to significant lifespan extension. PAR-1, a highly conserved serine/threonine kinase, functions as a key cellular polarity regulator during the embryonic development. However, the role of PAR-1 during adulthood remains unknown. Here we show that inhibition of [i]par-1[/i] either by a temperature-sensitive mutant or by RNAi knockdown only during adulthood is sufficient to extend lifespan in [i]C. elegans[/i]. Inhibition of [i]par-1[/i] also improves healthspan, as indicated by increased stress resistance, enhanced proteotoxicity resistance, as well as reduced muscular function decline over time. Additionally, tissue-enriched RNAi knockdown analysis reveals that PAR-1 mainly functions in the epidermis to regulate lifespan. Further genetic epistatic and molecular studies demonstrate that the effect of [i]par-1[/i] on lifespan requires the AMP-activated protein kinase (AMPK), and RNAi knockdown of [i]par-1[/i] results in age-dependent AMPK activation and reduced lipid accumulation in the metabolic tissue. Taken together, our findings reveal a previously undescribed function of PAR-1 in adulthood, which will help to understand the molecular links between development and aging.

MeSH Terms

-

Keywords

AMPK; Caenorhabditis elegans; PAR-1; healthspan; longevity

Identification of Key Genes and Potential New Biomarkers for Ovarian Aging: A Study Based on RNA-Sequencing Data.

Abstract

Ovarian aging leads to reproductive and endocrine dysfunction, causing the disorder of multiple organs in the body and even declined quality of offspring's health. However, few studies have investigated the changes in gene expression profile in the ovarian aging process. Here, we applied integrated bioinformatics to screen, identify, and validate the critical pathogenic genes involved in ovarian aging and uncover potential molecular mechanisms. The expression profiles of GSE84078 were downloaded from the Gene Expression Omnibus (GEO) database, which included the data from ovarian samples of 10 normal C57BL/6 mice, including old (21-22 months old, ovarian failure period) and young (5-6 months old, reproductive bloom period) ovaries. First, we filtered 931 differentially expressed genes (DEGs), including 876 upregulated and 55 downregulated genes through comparison between ovarian expression data from old and young mice. Functional enrichment analysis showed that biological functions of DEGs were primarily immune response regulation, cell-cell adhesion, and phagosome pathway. The most closely related genes among DEGs ([i]Tyrobp[/i], [i]Rac2[/i], [i]Cd14[/i], [i]Zap70[/i], [i]Lcp2[/i], [i]Itgb2[/i], [i]H2-Ab1[/i], and [i]Fcer1g[/i]) were identified by constructing a protein-protein interaction (PPI) network and consequently verified using mRNA and protein quantitative detection. Finally, the immune cell infiltration in the ovarian aging process was also evaluated by applying CIBERSORT, and a correlation analysis between hub genes and immune cell type was also performed. The results suggested that plasma cells and naïve CD4 T cells may participate in ovarian aging. The hub genes were positively correlated with memory B cells, plasma cells, M1 macrophages, Th17 cells, and immature dendritic cells. In conclusion, this study indicates that screening for DEGs and pathways in ovarian aging using bioinformatic analysis could provide potential clues for researchers to unveil the molecular mechanism underlying ovarian aging. These results could be of clinical significance and provide effective molecular targets for the treatment of ovarian aging.

MeSH Terms

-

Keywords

GEO database; bioinformatics; biomarker; immune cell infiltration; ovarian aging

Endoplasmic Reticulum Stress Mediates Vascular Smooth Muscle Cell Calcification via Increased Release of Grp78-Loaded Extracellular Vesicles.

Abstract

Vascular calcification is common among aging populations and mediated by vascular smooth muscle cells (VSMCs). The endoplasmic reticulum (ER) is involved in protein folding and ER stress has been implicated in bone mineralization. The role of ER stress in VSMC-mediated calcification is less clear. Approach and Results: mRNA expression of the ER stress markers PERK (PKR (protein kinase RNA)-like ER kinase), ATF (activating transcription factor) 4, ATF6, and Grp78 was detectable in human vessels with levels of PERK decreased in calcified plaques compared to healthy vessels. Protein deposition of Grp78/Grp94 was increased in the matrix of calcified arteries. Induction of ER stress accelerated human primary VSMC-mediated calcification, elevated expression of some osteogenic markers (Runx2, Osterix, ALP, BSP, and OPG), and decreased expression of SMC markers. ER stress potentiated extracellular vesicle (EV) release via SMPD3. EVs from ER stress-treated VSMCs showed increased Grp78 levels and calcification. Electron microscopy confirmed the presence of Grp78/Grp94 in EVs. siRNA knock-down of Grp78 decreased calcification. Warfarin-induced Grp78 and ATF4 expression in rat aortas and VSMCs and increased calcification in an ER stress-dependent manner via increased EV release. ER stress induces vascular calcification by increasing release of Grp78-loaded EVs. Our results reveal a novel mechanism of action of warfarin, involving increased EV release via the PERK-ATF4 pathway, contributing to calcification. This study is the first to show that warfarin induces ER stress and to link ER stress to cargo loading of EVs.

MeSH Terms

-

Keywords

aging; arteries; endoplasmic reticulum; vascular calcification; warfarin

Integrating music-based interventions with Gamma-frequency stimulation: Implications for healthy aging.

Abstract

In recent years, music-based interventions (MBIs) have risen in popularity as a non-invasive, sustainable form of care for treating dementia-related disorders, such as Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). Despite their clinical potential, evidence regarding the efficacy of MBIs on patient outcomes is mixed. Recently, a line of related research has begun to investigate the clinical impact of non-invasive Gamma-frequency (e.g., 40 Hz) sensory stimulation on dementia. Current work, using non-human-animal models of AD, suggests that non-invasive Gamma-frequency stimulation can remediate multiple pathophysiologies of dementia at the molecular, cellular, and neural-systems scales, and, importantly, improve cognitive functioning. These findings suggest that the efficacy of MBIs could, in theory, be enhanced by incorporating Gamma-frequency stimulation into current MBI protocols. In the current review, we propose a novel clinical framework for non-invasively treating dementia-related disorders that combines previous MBIs with current approaches employing Gamma-frequency sensory stimulation. We theorize that combining MBIs with Gamma-frequency stimulation could increase the therapeutic power of MBIs by simultaneously targeting multiple biomarkers of dementia, restoring neural activity that underlies learning and memory (e.g., Gamma-frequency neural activity, Theta-Gamma coupling), and actively engaging auditory and reward networks in the brain to promote behavioral change.

MeSH Terms

-

Keywords

Alzheimer’s disease; Gamma stimulation; aging; dementia; music-based interventions; neural oscillations

Associations of Lifestyle Factors With Cognition in Community-Dwelling Adults Aged 50 and Older: A Longitudinal Cohort Study.

Abstract

In the absence of an effective treatment to alter the progressive course of cognitive decline and dementia, identification of modifiable risk factors that could promote healthy cognitive aging has become a public health research priority. This study seeks to comprehensively determine the contemporaneous associations of a broad spectrum of time-varying modifiable lifestyle factors with age-related cognitive decline in a large population-based cohort of older adults. A total of 5,711 subjects aged 50 and older from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Repeated measures of lifestyle factors and cognitive performance were conducted in 2009-2010 and 2014-2015. Linear random slope models were used to evaluate the contemporaneous associations between time-varying lifestyle factors and cognitive performance. Person-mean centering method was used to disaggregate the between- and within-person effects in the time-varying lifestyle factors in the random slope models. We found that higher vegetable and fruit consumption, as well as higher level of physical activity were positively associated with all cognitive domains. Body mass index (BMI) was negatively associated with all cognitive domains, whereas waist-to-hip ratio (WHR) was negatively associated with verbal fluency score only. Sedentary time was negatively associated with digit span score but positively associated with verbal fluency score. The between-person effects seem to be more dominant than within-person effects. Overall, our findings suggest better management of multiple lifestyle factors may protect against cognitive decline in later life. Higher vegetable and fruit consumption and physical activity are protective, whereas obesity is detrimental to cognitive decline in older adults. This study underpins the development of multi-domain lifestyle recommendations to promote healthy cognitive aging.

MeSH Terms

-

Keywords

aging; cognitive decline; fruit; lifestyle; obesity; physical activity; sedentary time; vegetable

Cross-country differences in age trends in alcohol consumption among older adults: a cross-sectional study of individuals aged 50 years and older in 22 countries.

Abstract

Age-related changes in physiological, metabolic and medication profiles make alcohol consumption likely to be more harmful among older than younger adults. This study aimed to estimate cross-national variation in the quantity and patterns of drinking throughout older age, and to investigate country-level variables explaining cross-national variation in consumption for individuals aged 50 years and older. Cross-sectional observational study using previously harmonized survey data. Twenty-two countries surveyed in 2010 or the closest available year. A total of 106 180 adults aged 50 years and over. Cross-national variation in age trends were estimated for two outcomes: weekly number of standard drink units (SDUs) and patterns of alcohol consumption (never, ever, occasional, moderate and heavy drinking). Human Development Index and average prices of vodka were used as country-level variables moderating age-related declines in drinking. Alcohol consumption was negatively associated with age (risk ratio = 0.98; 95% confidence interval = 0.97, 0.99; P-value < 0.001), but there was substantial cross-country variation in the age-related differences in alcohol consumption [likelihood ratio (LR) test P-value < 0.001], even after adjusting for the composition of populations. Countries' development level and alcohol prices explained 31% of cross-country variability in SDUs (LR test P-value < 0.001) but did not explain cross-country variability in the prevalence of heavy drinkers. Use and harmful use of alcohol among older adults appears to vary widely across age and countries. This variation can be partly explained both by the country-specific composition of populations and country-level contextual factors such as development level and alcohol prices.

MeSH Terms

-

Keywords

Aging; alcohol; cross-cultural; development; drink; global; mixed model; multi-level; old age; price

What doesn't kill you makes you feel older: lifespan adversity and its association with subjective age among former prisoners of war.

Abstract

Subjective age (SA) is an indicator of aging that has been empirically associated with health impediments and hindered longevity. Studies show that adverse life events may result in relatively older SA, but have not addressed the differential contribution of life events across the lifespan and the course of posttraumatic psychopathology on the SA of aging survivors of extreme trauma.  : Filling this gap, the current study explored the differential contribution of (1) adverse experiences in various life-stages and (2) trajectories of posttraumatic stress disorder (PTSD) to the prediction of SA in a sample of former prisoners-of-war as they enter old age.  : A cohort of Israeli former prisoners-of-war of the 1973 Yom Kippur War ([i]N[/i] = 103) was assessed at four points throughout four decades after the war. A linear hierarchical regression was utilized to assess the contribution of negative life events during childhood, participation in other wars, combat exposure, suffering in captivity, life events since the war and the trajectories of PTSD for predicting SA 42-years post-repatriation.  : Lifespan adversity explained 50% of the variance in SA, with trajectories of PTSD making the largest contribution, followed by life events since the war. Negative life events in childhood added to the explained variance only when PTSD trajectories were accounted for. Exposure to combat, participation in additional wars and the severity of specific experiences during captivity did not reach significance, though the latter marginally contributed to the explained variance ([i]p[/i] [i]= [/i].069).  : This study demonstrates the importance of considering the prolongation of posttraumatic psychopathology together with life adversities and their differential implications when addressing SA after extreme trauma. The findings suggest that early life adversity may be a latent factor that increases vulnerability to posttraumatic premature aging processes.

MeSH Terms

-

Keywords

War trauma; aging process; captivity; negative life events; premature senescence

Mediators and Moderators of the Association Between Perceived Stress and Episodic Memory in Diverse Older Adults.

Abstract

Stress is a risk factor for numerous negative health outcomes, including cognitive impairment in late-life. The negative association between stress and cognition may be mediated by depressive symptoms, which separate studies have identified as both a consequence of perceived stress and a risk factor for cognitive decline. Pathways linking perceived stress, depressive symptoms, and cognition may be moderated by sociodemographics and psychosocial resources. The goal of this cross-sectional study was to identify modifying factors and enhance understanding of the mechanisms underlying the stress-cognition association in a racially and ethnically diverse sample of older adults. A linear regression estimated the association between perceived stress and episodic memory in 578 older adults (Mage = 74.58) in the Washington Heights-Inwood Columbia Aging Project. Subsequent models tested whether depressive symptoms mediated the stress-memory relationship and whether sociodemographics (gender, race, and ethnicity) or perceived control moderated these pathways. Independent of sociodemographics and chronic diseases, greater perceived stress was associated with worse episodic memory. This relationship was mediated by more depressive symptoms. Higher perceived control buffered the association between stress and depressive symptoms. There was no significant moderation by gender, race, or ethnicity. Depressive symptoms may play a role in the negative association between perceived stress and cognition among older adults; however, longitudinal analyses and studies using experimental designs are needed. Perceived control is a modifiable psychological resource that may offset the negative impact of stress.

MeSH Terms

-

Keywords

Cognitive aging; Depressive symptoms; Psychological stress; Sense of control

Testing a Proactive Model of Successful Aging Among Older Adults in Costa Rica and Spain.

Abstract

The purpose of this study is to examine successful aging among Spanish-speaking older adults in Costa Rica and in Spain using the proactive framework proposed by Kahana et al. (2014). More specifically, we hypothesized that older adults' life satisfaction would be positively associated with the frequency and perceived level of social support, spirituality/having purpose in life, and the use of proactive physical, cognitive, and social self-care behaviors. Our results confirmed these hypotheses, not only for the overall group of participants, but also separately for older adults in Costa Rica and in Spain. The present study contributes to the literature of successful aging among older adults, by examining the protective factors associated with life satisfaction among Spanish speaking older adults in Costa Rica and in Spain. It identifies specific protective factors (spirituality/purpose in life, social support, and self-care) associated with the values and preferences held by participants in the study.

MeSH Terms

-

Keywords

behavioral adaptations; life satisfaction; successful aging

Improving trainee engagement in science: Lessons from a virtual seminar series.

Abstract

To be a successful researcher, you are expected to have important skills beyond the bench such as being able to ask questions, talk about science with your peers, and organize scientific events. However, there is frequently little to no training or emphasis on these skills at the student and postdoc level. The virtual Aging Science Talks seminar series and Slack group have benefitted the scientific community in many ways amidst the chaos of coronavirus quarantines and lab shutdowns, but as a 2 year PhD student, I was particularly excited about how this format was able to engage trainees. We should end the era of trainees sitting at the back of the room while PIs dominate discussions and Q&A sessions with speakers. Reflecting on the advantages of Aging Science Talks can show us how to make future scientific events more engaging and inclusive for everyone.

MeSH Terms

-

Keywords

Aging science talks; Remote work; Students; Trainees

A guide for medical practitioners transitioning to an encore career or retirement.

Abstract

---

MeSH Terms

-

Keywords

Aging; Clinical competence

Structural complexity is negatively associated with brain activity: a novel multimodal test of compensation theories of aging.

Abstract

Fractal dimensionality (FD) measures the complexity within the folds and ridges of cortical and subcortical structures. We tested the degree that FD might provide a new perspective on the atrophy-compensation hypothesis: age or disease-related atrophy causes a compensatory neural response in the form of increased brain activity in the prefrontal cortex to maintain cognition. Brain structural and functional data were collected from 63 middle-aged and older adults and 18 young-adult controls. Two distinct patterns of FD were found that separated cortical from subcortical structures. Subcortical FD was more strongly negatively correlated with age than cortical FD, and cortical FD was negatively associated with brain activity during memory retrieval in medial and lateral parietal cortices uniquely in middle-aged and older adults. Multivariate analyses revealed that the lower FD/higher brain activity pattern was associated with poorer cognition-patterns not present in young adults, consistent with compensation. Bayesian analyses provide further evidence against the modal interpretation of the atrophy-compensation hypothesis in the prefrontal cortex-a key principle found in some neurocognitive theories of aging.

MeSH Terms

-

Keywords

Aging; Compensation; Default mode network; Episodic memory; Fractal dimensionality; fMRI

Assessing the Effect of Training on the Cognition and Brain of Older Adults: Protocol for a Three-Arm Randomized Double-Blind Controlled Trial (ACTOP).

Abstract

To prevent age-related cognitive impairment, many intervention programs offer exercises targeting different central cognitive processes. However, the effects of different process-based training programs are rarely compared within equivalent experimental designs. Using a randomized double-blind controlled trial, this project aims to examine and compare the impact of 2 process-based interventions, inhibition and updating, on the cognition and brain of older adults. A total of 90 healthy older adults were randomly assigned to 1 of 3 training conditions: (1) inhibition (Stroop-like exercises), (2) updating (N-back-type exercises), and (3) control active (quiz game exercise). Training was provided in 12 half-hour sessions over 4 weeks. First, the performance gain observed will be measured on the trained tasks. We will then determine the extent of transfer of gain on (1) untrained tasks that rely on the same cognitive process, (2) complex working memory (WM) measurements hypothesized to involve 1 of the 2 trained processes, and (3) virtual reality tasks that were designed to mimic real-life situations that require WM. We will assess whether training increases cortical volume given that the volume of the cortex is determined by cortical area and thickness in regions known to be involved in WM or changes task-related brain activation patterns measured with functional magnetic resonance imaging. Dose effects will be examined by measuring outcomes at different time points during training. We will also determine whether individual characteristics moderate the effect of training on cognitive and cerebral outcomes. Finally, we will evaluate whether training reduces the age-related deficit on transfer and brain outcomes, by comparing study participants to a group of 30 younger adults. The project was funded in January 2017; enrollment began in October 2017 and data collection was completed in April 2019. Data analysis has begun in June 2020 and the first results should be published by the end of 2020 or early 2021. The results of this study will help understand the relative efficacy of 2 attentional control interventions on the cognition and the brain of older adults, as well as the moderating role of individual characteristics on training efficiency and transfer. ClinicalTrials.gov NCT03532113; https://clinicaltrials.gov/ct2/show/NCT03532113. DERR1-10.2196/20430.

MeSH Terms

-

Keywords

aging; brain plasticity; cognitive reserve; cognitive training; working memory

Interactions of iron-based nanoparticles with soil dissolved organic matter: adsorption, aging, and effects on hexavalent chromium removal.

Abstract

The interactions and mechanisms between soil dissolved organic matter (DOM) and three types of iron-based nanoparticles (NPs), i.e., nanoscale zero-valent iron (nZVI) particles, Fe O NPs, and Fe O NPs, were investigated in short-term exposure experiments. The adsorption results showed that soil DOM was rapidly adsorbed on the surface of the iron-based NPs with the adsorption rate varying according to Fe O > Fe O > nZVI. Spectral analysis results revealed that aromatic DOM fractions with high-molecular-weights were preferentially adsorbed. The binding mechanism was determined as hydrogen bonding and ligand exchange via Fourier transform infrared spectroscopy (FT-IR) analysis. Scanning electron microscopy, FT-IR, X-ray photoelectron spectroscopy, and X-ray diffraction were used to identify the corrosion products of the three iron-based NPs at the adsorption equilibrium. The results suggest that Fe O and/or γ-Fe O and α-FeOOH were the main corrosion products of nZVIs and α-FeOOH was obtained as an aged product of Fe O NPs. Results of Cr(VI) removal tests suggest that the aged nZVI achieved 79.87% of Cr(VI) removal and the Cr(VI) removal efficiency was significantly improved by coating DOM onto Fe O NPs. The overall data indicate the fate and transformation of iron-based NPs and the enhancement for Cr(VI) removal after interactions between DOM and NPs.

MeSH Terms

-

Keywords

Adsorption; Aging products; Binding mechanism; Iron-based NPs; Soil DOM

Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression.

Abstract

Sestrin2 (Sesn2) is involved in the maintenance of metabolic homeostasis and aging via modulation of the 5' AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) pathway. Wild-type and Sesn2 knockout (KO) mice of the 129/SvJ background were maintained in a pathogen-free authorized facility under a 12-hour dark/light cycle at 20°C-22°C and 50%-60% humidity. Mouse embryonic fibroblasts (MEFs) were prepared from 13.5-day-old embryos derived from Sesn2-KO mice mated with each other. The MEFs from Sesn2-KO mice showed enlarged and flattened morphologies and senescence-associated β-galactosidase activity, accompanied by an elevated level of reactive oxygen species. These senescence phenotypes recovered following treatment with N-acetyl-cysteine. Notably, the mRNA levels of NADPH oxidase 4 (NOX4) and transforming growth factor (TGF)-β were markedly increased in Sesn2-KO MEFs. Treatment of Sesn2-KO MEFs with the NOX inhibitor diphenyleneiodonium and the TGF-β inhibitor SB431542 restored cell growth inhibited by Sesn2-KO. Sesn2 attenuates cellular senescence via suppression of TGF-β- and NOX4-induced reactive oxygen species generation and subsequent inhibition of AMPK.

MeSH Terms

-

Keywords

NOX4; Reactive oxygen species; Senescence; Sestrin2

Geometrical model for calculating the effect of surface morphology on total x-ray output of medical x-ray tubes.

Abstract

Correlation of characteristic surface appearance and surface roughness with measured air kerma (kinetic energy released in air) reduction of WRe stationary anode surfaces. A stationary anode test system was developed and used to alter nine initially ground sample surfaces through thermal cycling at high temperatures. A geometrical model based on high resolution surface data was implemented to correlate the measured reduction of the air kerma rate with the changing surface appearance of the samples. In addition to the nine thermally cycled samples, three samples received synthetic surface structuring to prove the applicability of the model to non-conventional surface alterations. Representative surface data and surface roughness values were acquired by laser scanning confocal microscopy. After thermal cycling in the stationary anode test system, the samples showed surface features comparable to rotating anodes after long-time operation. The established model enables the appearance of characteristic surface features like crack networks, pitting and local melting to be linked to the local x-ray output at 100 kV tube voltage, 10° anode take off angle and 2 mm of added Al filtration. The results from the conducted air kerma measurements were compared to the predicted total x-ray output reduction from the geometrical model and show, on average, less than 10 % error within the 12 tested samples. In certain boundaries, the calculated surface roughness R showed a linear correlation with the measured air kerma reduction when samples were having comparable damaging characteristics and similar operation parameters. The orientation of the surface features had a strong impact on the measured air kerma rate which was shown by testing synthetically structured surfaces. The geometrical model used herein considers and describes the effect of individual surface features on the x-ray output. In close boundaries arithmetic surface roughness R was found to be a useful characteristic value on estimating the effect of surface damage on total x-ray output.

MeSH Terms

-

Keywords

Surface damage; laser scanning confocal microscopy; rotating anode; surface roughening; tube aging; tungsten; x-ray tube

Hypoperfusion is a potential inducer of immunosuppressive network in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease which causes a non-reversible cognitive impairment and dementia. The primary cause of late-onset AD remains unknown although its pathology was discovered over a century ago. Recently, the vascular hypothesis of AD has received backing from evidence emerging from neuroimaging studies which have revealed the presence of a significant hypoperfusion in the brain regions vulnerable to AD pathology. In fact, hypoxia can explain many of the pathological changes evident in AD pathology, e.g. the deposition of β-amyloid plaques and chronic low-grade inflammation. Hypoxia-inducible factor-1α (HIF-1α) stimulates inflammatory responses and modulates both innate and adaptive immunity. It is known that hypoxia-induced inflammation evokes compensatory anti-inflammatory response involving tissue-resident microglia/macrophages and infiltrated immune cells. Hypoxia/HIF-1α induce immunosuppression by (i) increasing the expression of immunosuppressive genes, (ii) stimulating adenosinergic signaling, (iii) enhancing aerobic glycolysis, i.e. lactate production, and (iv) augmenting the secretion of immunosuppressive exosomes. Interestingly, it seems that these common mechanisms are also involved in the pathogenesis of AD. In AD pathology, an enhanced immunosuppression appears, e.g. as a shift in microglia/macrophage phenotypes towards the anti-inflammatory M2 phenotype and an increase in the numbers of regulatory T cells (Treg). The augmented anti-inflammatory capacity promotes the resolution of acute inflammation but persistent inflammation has crucial effects not only on immune cells but also harmful responses to the homeostasis of AD brain. I will examine in detail the mechanisms of the hypoperfusion/hypoxia-induced immunosuppressive state in general and especially, in its association with AD pathogenesis. These immunological observations support the vascular hypothesis of AD pathology.

MeSH Terms

-

Keywords

Ageing; Cerebral blood flow; Immunometabolism; Immunosenescence; MDSC; Neurovascular unit

Numeracy Skills, Cognitive Reserve, and Psychological Well-Being: What Relationship in Late Adult Lifespan?

Abstract

The capacity of understanding and manipulating numerical stimuli (i.e., numeracy) can impact decision making. This investigation was conducted to examine whether number comprehension and mental calculation predict hedonic (i.e., Scale of Positive and Negative Experience, SPANE) and eudaimonic (i.e., Flourishing Scale) well-being in late adulthood, and whether cognitive reserve (i.e., education, time spent for gardening, and time spent for leisure activities) and non-verbal reasoning predict numeracy skills of old adults. Additionally, the effect of age on numeracy was examined, controlling for the effect of education and cognitive efficiency. One hundred and fifty-eight (i.e., 65-94 years old) community-dwellers completed a battery of tools assessing numeracy, cognitive and metacognitive efficiency, and psychological well-being. Number comprehension, metacognition, time spent for leisure, and perceived physical health accounted for 23% of the variance in the SPANE condition, whereas metacognition, perceived physical health, time for leisure, and education explained 15% of the variance in the Flourishing condition. Moreover, cognitive reserve assessed in terms of vocabulary and education predicted mental calculation. Finally, aging significantly impacted the mental calculation performance of older participants. These findings suggest that numeracy skills can selectively impact the mental health and daily life of older adults.

MeSH Terms

-

Keywords

aging; cognitive reserve; mental calculation; mental health; metacognition; number comprehension; numeracy; physical health; psychological well-being

Eczema in elderly people.

Abstract

Eczema is one of the most common reasons for consultation in older people. Many differential diagnoses must be eliminated, including scabies, bullous pemphigoid, and mycosis fungoides. Contact dermatitis may also be considered and the chemical(s) in question may vary according to the comorbidities involved, in particular, depending on whether or not the patient has a leg ulcer. Drug-induced eczematous eruptions can occur in elderly people, mainly with antihypertensive drugs (calcium inhibitors, diuretics, etc.). Recently, de novo atopic dermatitis has been described in elderly subjects, and the role of pollution has been evoked for these eczemas. Management of eczema in the elderly is challenging, and emollients and dermocorticosteroids are helpful. However, local corticosteroids may have some adverse effects in this vulnerable population, such as skin atrophy, diabetes and hypertension. Phototherapy, when possible, and low-dose methotrexate in particular may be interesting treatment options.

MeSH Terms

-

Keywords

atopic dermatitis; drug hypersensitivity; eczema; elderly; skin aging

Building and Sustaining a Community Advisory Board of African American Older Adults as the Foundation for Volunteer Research Recruitment and Retention in Health Sciences.

Abstract

Older African Americans' participation in health-related research is severely limited; they are not involved in sufficient numbers to ensure the applicability of advancements in medical and behavioral health. This research participation gap exacerbates older African Americans' vulnerability to poor health outcomes and disparities. The Michigan Center for Urban African American Aging Research employs a progressive community-based participatory model that utilizes a structured community advisory board (CAB) of African American older adults in metro Detroit, Michigan to oversee the research recruitment and retention of fellow minority older adult research participants. CAB members develop and support community health programming that provides free resources to older adults and also serves as fertile ground for recruiting participants in a volunteer research registry. CAB members are also provided ongoing training on social and behavioral health research and are supported in acting as a consultancy to outside researchers where they can be compensated for their expertise and engagement. This community-engaged model of sustaining a CAB of African American older adults offers key lessons learned on building relationships and trust, valuing and leveraging community members' expertise and time, sharing decision-making, and fostering genuine community all while promoting research recruitment and retention among underserved populations.

MeSH Terms

-

Keywords

African American; Aging; Community-based Participatory Approach; Research Recruitment

Low Self-Perception of Malnutrition in Older Hospitalized Patients.

Abstract

Studies focusing on self-perception of nutritional status in older hospitalized patients are lacking. We aimed to examine the self-perception of body weight and nutritional status among older hospitalized patients compared to their actual body weight and nutritional status based on medical assessment. This observational cross-sectional study investigated 197 older participants (mean age 82.2±6.8 years, 61% women) who were consecutively admitted to the geriatric acute care ward. Body weight status and nutritional status were assessed using WHO-BMI classification and Mini Nutritional Assessment-Short Form (MNA-SF), respectively. Self-perceived body weight status and nutritional status were assessed with a standardized questionnaire. A follow-up was performed with a short telephone interview after three months. According to MNA-SF, 49% and 35% were at risk of malnutrition and malnourished, respectively. There was no agreement between self-perceived nutritional status and objective nutritional status according to MNA-SF (Kappa: 0.06). A slight agreement was found between subjective body weight status and objective body weight status according to WHO-BMI classification (Kappa: 0.19). A total of 184 patients completed the 3 months follow-up and additional 9 patients died during this time, of which 7 and 2 were malnourished and at risk of malnutrition according to MNA-SF, respectively. Of those who were malnourished and at risk of malnutrition based on MNA-SF and died during follow-up, 67.7% did not realize their malnutrition. Compared to the patients with normal nutritional status during hospitalization, malnourished patients based on MNA-SF had higher rates of unplanned hospital readmission and further weight loss and more often reported health deterioration and experienced death within three months after discharge. No agreement between self-perceived nutritional status and objective nutritional status among older hospitalized patients was found. Our study highlights the need to raise knowledge about the issue of malnutrition and increase awareness of health risks associated with malnutrition among older hospitalized patients.

MeSH Terms

-

Keywords

body weight; geriatrics; malnutrition; older patients; self-perception

Breed-related expression patterns of Ki67, γH2AX, and p21 during ageing in the canine liver.

Abstract

Cellular senescence is a molecular hallmark of ageing that is associated with multiple pathologies, and DNA damage marker γH2AX, together with cell cycle inhibitor p21, have been used as senescence markers in multiple species including dogs. Idiopathic canine chronic hepatitis has recognised breed-related differences in predisposition and prognosis, but reasons behind this are poorly understood. This retrospective study using archived post mortem tissue aimed to provide insight into liver ageing in 51 microscopically normal canine livers across seven breed categories, including those with and without increased risk of chronic hepatitis. Immunohistochemistry was conducted for γH2AX, p21, and cell proliferation marker Ki67, and the mean number of positive hepatocytes per high power field was determined. All three markers were strongly correlated to each other, but no age-dependent expression was seen in the combined study population. Overall expression levels were low in most dogs, with median values representing less than 1.5% of hepatocytes, but this increased to 20-30% in individual dogs at the upper end of the range. Individual breed differences were noted in two breeds that have increased risk of chronic hepatitis, with English Springer Spaniels having lower expression of Ki67 than other dogs, and Labradors having higher expression of Ki67 and γH2AX than other dogs. These results warrant further investigation in these breeds and highlight a need to validate reliable markers of cellular senescence in dogs.

MeSH Terms

-

Keywords

Ageing; Canine; Ki67; Liver; Senescence

Volunteer service and positive attitudes toward aging among Chinese older adults: The mediating role of health.

Abstract

Attitude toward aging is an important indicator for measuring the wellbeing of older people, and a vital part of active and healthy aging. We aimed to assess the relationship between volunteer service and attitudes toward aging held by older people and to determine the mediating role of health. We analyzed the data of 10,792 Chinese people over age 60 from the 2014 Chinese Longitudinal Aging Social Survey. We used multiple linear regression models and the two-stage least-squares model to explore the correlation between volunteer service and attitudes toward aging. Furthermore, we applied structural equation modeling to test for mediation effects of different aspects of health. We found that volunteer service was significantly associated with attitudes toward aging (β = 0.335, p < 0.001), while self-assessed health, physical health, and mental health played a mediating role between volunteer service and attitudes toward aging held by older adults. In exploring ways to cope with the challenges brought about by the aging of the population, we found that participating in volunteer services not only improves older people's self-assessed physical, and mental health, but also improves their positive attitudes toward aging. Therefore, under the framework of active and healthy aging, volunteer service and participation in social activities can enhance social vitality and welfare, reduce social burden, and improve quality of life.

MeSH Terms

-

Keywords

Attitude toward aging; Chinese; Mental health; Older people; Physical health; Self-assessed health; Volunteer service

Functional Connectivity of Successful Picture-Naming: Age-Specific Organization and the Effect of Engaging in Stimulating Activities.

Abstract

Aging is a lifelong process that starts at birth. Throughout the course of their life, individuals are exposed to various levels of stimulating activities. A higher level of engagement in such activities is suspected to protect against the normal course of cognitive aging or the cognitive manifestations of age-related brain diseases. However, the exact mechanism underlying such protective action remains unclear. The concept of the neurocognitive reserve was introduced to refer to the hypothesis that engagement in stimulating activities shapes brain structure and function, thus indirectly allowing for better preserved cognitive abilities. Although it is known that word production is among the best-preserved cognitive abilities in aging, the underlying neurofunctional mechanisms that allow this relative preservation are still unknown, and it is still unclear how engagement in stimulating activities affects these processes. The objective of this study is to describe the brain functional connectivity patterns associated with picture-naming abilities in younger and older adults with varying levels of engagement in stimulating activities, as a proxy for neurocognitive reserve. A mediation analysis was applied to determine whether the association between reserve proxies and naming accuracy is dependent on task FC. Results show that naming accuracy depends on the posterior cingulate cortex (PCC) functional decoupling in both younger and older adults but through different pathways. While high-performing older adults rely on the asynchronization of this area from motor speech regions' activity, the best-performing younger adults rely on the functional decoupling with language-related regions. Mediation analysis reveals that the PCC decoupling mediates the relationship between the level of engagement in stimulating activities and naming accuracy in younger adults, but not in older adults. These findings suggest that reserve-related mechanisms may be more critical for naming in early adult life, while older adults' neurofunctional organization may benefit more from a lifetime of acquired knowledge.

MeSH Terms

-

Keywords

aging; cognitive reserve; functional connectivity; mediation analysis; picture-naming

Sirtuins and Their Implications in Neurodegenerative Diseases from a Drug Discovery Perspective.

Abstract

Sirtuins are class III histone deacetylase (HDAC) enzymes that target both histone and non-histone substrates. They are linked to different brain functions and the regulation of different isoforms of these enzymes is touted to be an emerging therapy for the treatment of neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). The level of sirtuins affects brain health as many sirtuin-regulated pathways are responsible for the progression of NDs. Certain sirtuins are also implicated in aging, which is a risk factor for many NDs. In addition to SIRT1-3, it has been suggested that the less studied sirtuins (SIRT4-7) also play critical roles in brain health. This review delineates the role of each sirtuin isoform in NDs from a disease centric perspective and provides an up-to-date overview of sirtuin modulators and their potential use as therapeutics in these diseases. Furthermore, the future perspectives for sirtuin modulator development and their therapeutic application in neurodegeneration are outlined in detail, hence providing a research direction for future studies.

MeSH Terms

-

Keywords

Aging; neurodegenerative diseases; neuroprotective; sirtuin; sirtuin activators; sirtuin inhibitors

Short communication: Evidence for the 'rate-of-living' hypothesis between mammals and lizards not in birds, with field metabolic rate.

Abstract

Longevity, an important life-history trait, is determined by extrinsic, intrinsic, or both factors causing mortality. Here, we used body mass (BM), field metabolic rate (FMR), longevity, and female maturity data reported from 300 amniote species to test whether 1) longevity was related to BM, FMR and female maturity, and 2) FMR, female maturity, or both, had a direct effect on longevity and whether an indirect effect of FMR on female maturity improved model fit. The results showed that BM was positively related to longevity and FMR, but negatively related to mass-specific FMR (mFMR) in amniotes. In the best model, phylogenetic path analysis showed that longevity had a direct negatively correlation with mFMR in lizards, and longevity had an indirect negatively correlation with mFMR through female maturity in mammals. However, longevity had a direct positively correlation with mFMR in birds. Furthermore, longevity had a positive correlation associating longevity with female maturity in endotherms (birds and mammals) but only a weak correlation with female maturity in ectotherms (lizards). Our results supported the life-history theory and the 'rate-of-living' hypothesis in lizards and mammals but did not support them in birds.

MeSH Terms

-

Keywords

Amniote; Field metabolic rate; Life history; Longevity

Association between a Deficit Accumulation Frailty Index and Mobility Outcomes in Older Adults: Secondary Analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study.

Abstract

Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score's quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1-5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2-5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.

MeSH Terms

-

Keywords

LIFE Study; deficit accumulation; disability; frailty; healthy aging; mobility; older adults

Prevalent intron retention fine-tunes gene expression and contributes to cellular senescence.

Abstract

Intron retention (IR) is the least well-understood alternative splicing type in animals, and its prevalence and function in physiological and pathological processes have long been underestimated. Cellular senescence contributes to individual aging and age-related diseases and can also serve as an important cancer prevention mechanism. Dynamic IR events have been observed in senescence models and aged tissues; however, whether and how IR impacts senescence remain unclear. Through analyzing polyA RNA-seq data from human replicative senescence models, we found IR was prevalent and dynamically regulated during senescence and IR changes negatively correlated with expression alteration of corresponding genes. We discovered that knocking down (KD) splicing factor U2AF1, which showed higher binding density to retained introns and decreased expression during senescence, led to senescence-associated phenotypes and global IR changes. Intriguingly, U2AF1-KD-induced IR changes also negatively correlated with gene expression. Furthermore, we demonstrated that U2AF1-mediated IR of specific gene (CPNE1 as an example) contributed to cellular senescence. Decreased expression of U2AF1, higher IR of CPNE1, and reduced expression of CPNE1 were also discovered in dermal fibroblasts with age. We discovered prevalent IR could fine-tune gene expression and contribute to senescence-associated phenotypes, largely extending the biological significance of IR.

MeSH Terms

-

Keywords

CPNE1; U2AF1; intron retention; senescence; splicing factor

Acute, exercise-induced alterations in cytokines and chemokines in the blood distinguish physically active and sedentary aging.

Abstract

Aging results in a chronic, pro-inflammatory state which can promote and exacerbate age-associated diseases. In contrast, physical activity in older adults improves whole body health, protects against disease, and reduces inflammation, but the elderly are less active making it difficult to disentangle the effects of aging from a sedentary lifestyle. To interrogate this interaction, we analyzed peripheral blood collected at rest and post-exercise from 68 healthy younger and older donors that were either physically active aerobic exercisers or chronically sedentary. Subjects were profiled for 44 low-abundance cytokines, chemokines and growth factors in peripheral blood. At rest, we found that regular physical activity had no impact on the age-related elevation in circulating IL-18, eotaxin, GRO, IL-8, IP-10, PDGF-AA or RANTES. Similarly, there was no impact of physical activity on the age-related reduction in VEGF, EGF or IL-12 (p70). However, older exercisers had lower resting plasma fractalkine, IL-3, IL-6 and TNF-α compared to sedentary older adults. In contrast to our resting characterization, blood responses following acute exercise produced more striking difference between groups. Physically active younger and older subjects increased over 50% of the analyzed factors in their blood which resulted in both unique and overlapping exercise signatures. However, sedentary individuals, particularly the elderly, had few detectable changes in response to exercise. Overall, we show that long term physical activity has a limited effect on age-associated changes in basal cytokines and chemokines in the healthy elderly, yet physically active individuals exhibit a broader induction of factors post-exercise irrespective of age.

MeSH Terms

-

Keywords

growth factors; human aging; inflammation; physical activity

Middle age as a turning point in mouse cerebral cortex energy and redox metabolism: Modulation by every-other-day fasting.

Abstract

Normal brain aging is accompanied by intensification of free radical processes and compromised bioenergetics. Caloric restriction is expected to counteract these changes but the underlying protective mechanisms remain poorly understood. The present work aimed to investigate the intensity of oxidative stress and energy metabolism in the cerebral cortex comparing mice of different ages as well as comparing mice given one of two regimens of food availability: ad libitum versus every-other-day fasting (EODF). Levels of oxidative stress markers, ketone bodies, glycolytic intermediates, mitochondrial respiration, and activities of antioxidant and glycolytic enzymes were assessed in cortex from 6-, 12- and 18-month old C57BL/6 J mice. The greatest increase in oxidative stress markers and the sharpest decline in key glycolytic enzyme activities was observed in mice upon the transition from young (6 months) to middle (12 months) age, with smaller changes occurring upon transition to old-age (18 months). Brain mitochondrial respiration showed no significant changes with age. A decrease in the activities of key glycolytic enzymes was accompanied by an increase in the activity of glucose-6-phosphate dehydrogenase suggesting that during normal brain aging glucose metabolism is altered to lower glycolytic activity and increase dependence on the pentose-phosphate pathway. Interestingly, levels of ketone bodies and antioxidant capacity showed a greater decrease in the brain cortex of females as compared with males. The EODF regimen further suppressed glycolytic enzyme activities in the cortex of old mice, and partially enhanced oxygen consumption and respiratory control in the cortex of middle aged and old males. Thus, in the mammalian cortex the major aging-induced metabolic changes are already seen in middle age and are slightly alleviated by an intermittent fasting mode of feeding.

MeSH Terms

-

Keywords

Aging; Antioxidant enzymes; Cerebral cortex; Glycolytic enzymes; Mitochondrial respiration; Pentose phosphate pathway

Early brainstem [18F]THK5351 uptake is linked to cortical hyper-excitability in healthy aging.

Abstract

Neuronal hyper-excitability characterizes the early stages of Alzheimer's disease (AD). In animals, early misfolded tau and amyloid-beta (Aβ) protein accumulation, both central to AD neuropathology, promote cortical excitability and neuronal network dysfunction. In healthy humans, misfolded tau and Aβ aggregates are first detected, respectively, in the brainstem and frontomedial and temporobasal cortices, decades prior to the onset of AD cognitive symptoms. Whether cortical excitability is related to early brainstem tau, and its associated neuroinflammation, and cortical Aβ aggregations remains unknown. We probed frontal cortex excitability, using transcranial magnetic stimulation combined with electroencephalography, in a sample of 64 healthy late middle-aged individuals (50-69 y; 45 women). We assessed whole-brain [18F]THK5351 positron emission tomography (PET) uptake as a proxy measure of tau/neuroinflammation, and whole-brain Aβ burden with [18F]Flutemetamol or [18F]Florbetapir radiotracers. We find that higher [18F]THK5351 uptake in a brainstem monoaminergic compartment is associated with increased cortical excitability (r = .29, p = .02). By contrast, [18F]THK5351 PET signal in the hippocampal formation, although strongly correlated with brainstem signal in whole-brain voxel-based quantification analyses (pFWE-corrected < .001), was not significantly associated with cortical excitability (r = .14, p = .25). Importantly, no significant association was found between early Aβ cortical deposits and cortical excitability (r = -.20, p = .11). These findings reveal potential brain substrates for increased cortical excitability in preclinical AD and may constitute functional in vivo correlates of early brainstem tau accumulation and neuroinflammation in humans. EudraCT 2016-001436-35. F.R.S.-FNRS Belgium, Wallonie-Bruxelles International, ULiège, Fondation Simone et Pierre Clerdent, European Regional Development Fund.

MeSH Terms

-

Keywords

Aging; Alzheimer's disease; Neuroimaging; Neuroscience

Suicide and Suicide Attempts in the Elderly Patients: An Epidemiological Analysis of Risk Factors and Prevention.

Abstract

Some elderly commit suicide due to the interaction of various factors including, for example, feelings of loneliness, financial distress, alcohol abuse, chronic pain, progressive diseases, and personality disorders. The data from the EU countries with the highest rates of suicide and suicide attempts among people over 55 years of age warrant the consideration of new approaches to address this social problem. PubMed and other databases including Polish National data were used for the analyses. The average European suicide-attempt rate is 18 per 100 thousand inhabitants. More cases of suicides were reported among those over 55 years of age. Suicide attempts from 2012 to 2014 and deaths in 2012 have been reviewed. The risk factors involved in these events such as, depression, social situation including loneliness, health condition, etc., have been discussed to suggest a plausible preventative approach for this important elderly problem. The psychophysiology of elderly persons affected by retirement, socio-economic changes, limited personal autonomy, loneliness, lack of support by the family, and diseases ultimately may lead elderly persons to commit suicide. Thus, financial freedom, family support (respect, love, and care), proper medications, psychological, and psychiatric interventions may help the elderly avoid suicidal thoughts and prevent attempts.

MeSH Terms

-

Keywords

chronic pain; elderly; geriatrics; gerontology; life quality.; personality disorder; psyhcology; suicide and suicide attempt

Clinical outcomes in patients admitted to hospital with cervical spine fractures or with hip fractures.

Abstract

Patients admitted with a cervical fracture are twice as likely to die within 30 days of injury than those with a hip fracture. However, guidelines for the management of cervical fractures are less available than for hip fractures. We hypothesise that outcomes may differ between these types of fractures. We analysed 1359 patients (406 men, 953 women) with mean age of 83.8 years (standard deviation = 8.7) admitted to a National Health Service hospital in 2013-2019 with a cervical (7.5%) or hip fracture (92.5%) of similar age. The association of cervical fracture (hip fracture as reference), hospital length of stay (LOS), co-morbidities, age and sex with outcomes (acute delirium, new pressure ulcer, and discharge to residential/nursing care) was assessed by stepwise multivariate logistic regression. Acute delirium without history of dementia was increased with cervical fractures: odds ratio (OR) = 2.4, 95% confidence interval (CI) = 1.3-4.7, age ≥ 80 years: OR = 3.5 (95% CI = 1.9-6.4), history of stroke: OR = 1.8 (95% CI = 1.0-3.1) and ischaemic heart disease: OR = 1.9 (95% CI = 1.1-3.6); pressure ulcers was increased with cervical fractures: OR = 10.9 (95% CI = 5.3-22.7), LOS of 2-3 weeks: OR = 3.0 (95% CI = 1.2-7.5) and LOS of ≥ 3 weeks: OR = 4.9, 95% CI = 2.2-11.0; and discharge to residential/nursing care was increased with cervical fractures: OR = 3.2 (95% CI = 1.4-7.0), LOS of ≥ 3 weeks: OR = 4.4 (95% CI = 2.5-7.6), dementia: OR = 2.7 (95% CI = 1.6-4.7), Parkinson's disease: OR = 3.4 (95% CI = 1.3-8.8), and age ≥ 80 years: OR = 2.7 (95% CI = 1.3-5.6). In conclusion, compared with hip fracture, cervical fracture is more likely to associate with acute delirium and pressure ulcers, and for discharge to residency of high level of care, independent of established risk factors.

MeSH Terms

-

Keywords

Discharge destination; Geriatrics; Length of stay; Mortality; Pressure ulcers

Longevity record of arctic skua ([i]Stercorarius parasiticus[/i]).

Abstract

The arctic skua ([i]Stercorarius parasiticus[/i]) is one of the most long-lived bird species. In 2010, we captured in Finland an adult, female arctic skua which had been ringed as a nestling in 1987. We tagged it also with a color ring. The bird has last been seen in July 2020 at the age of 33 years, making it most likely the oldest known arctic skua of the world. In 2010-2011 the bird carried a light-level measuring geolocator, the data of which revealed that the bird had spent the nonbreeding season in the Canary Current area on the west coast of Africa. Breeding populations of arctic skuas have declined recently especially in British Isles, thus it is useful to get longevity data of this species with a high breeding site fidelity.

MeSH Terms

-

Keywords

arctic skua; breeding; geolocator; longevity; migration; seabird

A Comprehensive Analysis of Age and Gender Effects in European Portuguese Oral Vowels.

Abstract

The knowledge about the age effects in speech acoustics is still disperse and incomplete. This study extends the analyses of the effects of age and gender on acoustics of European Portuguese (EP) oral vowels, in order to complement initial studies with limited sets of acoustic parameters, and to further investigate unclear or inconsistent results. A database of EP vowels produced by a group of 113 adults, aged between 35 and 97, was used. Duration, fundamental frequency (f0), formant frequencies (F1 to F3), and a selection of vowel space metrics (F1 and F2 range ratios, vowel articulation index [VAI] and formant centralization ratio [FCR]) were analyzed. To avoid the arguable division into age groups, the analyses considered age as a continuous variable. The most relevant age-related results included: vowel duration increase in both genders; a general tendency to formant frequencies decrease for females; changes that were consistent with vowel centralization for males, confirmed by the vowel space acoustic indexes; and no evidence of F3 decrease with age, in both genders. This study has contributed to knowledge on aging speech, providing new information for an additional language. The results corroborated that acoustic characteristics of speech change with age and present different patterns between genders.

MeSH Terms

-

Keywords

Acoustic; Aging voice; European Portuguese; Oral vowel

Senescence and the SASP: many therapeutic avenues.

Abstract

Cellular senescence is a stress response that elicits a permanent cell cycle arrest and triggers profound phenotypic changes such as the production of a bioactive secretome, referred to as the senescence-associated secretory phenotype (SASP). Acute senescence induction protects against cancer and limits fibrosis, but lingering senescent cells drive age-related disorders. Thus, targeting senescent cells to delay aging and limit dysfunction, known as "senotherapy," is gaining momentum. While drugs that selectively kill senescent cells, termed "senolytics" are a major focus, SASP-centered approaches are emerging as alternatives to target senescence-associated diseases. Here, we summarize the regulation and functions of the SASP and highlight the therapeutic potential of SASP modulation as complimentary or an alternative to current senolytic approaches.

MeSH Terms

-

Keywords

SASP; aging; cancer; disease; inflammation; senescence; senolytics; senomorphics; therapeutics

Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle.

Abstract

Aging is an evolutionally conserved process that limits life activity. Cellular aging is the result of accumulated genetic damage, epigenetic damage and molecular exhaustion, as well as altered inter-cellular communication; these lead to impaired organ function and increased vulnerability to death. Skeletal muscle constitutes ~40% of the human body's mass. In addition to maintaining skeletal structure and allowing locomotion, which enables essential daily activities to be completed, skeletal muscle also plays major roles in thermogenesis, metabolism and the functioning of the endocrine system. Unlike many other organs that have a defined size once adulthood is reached, skeletal muscle is able to alter its structural and functional properties in response to changes in environmental conditions. Muscle mass usually remains stable during early life; however, it begins to decline at a rate of ~1% year in men and ~0.5% in women after the age of 50 years. On the other hand, different exercise training regimens are able to restore muscle homeostasis at the molecular, cellular and organismal levels, thereby improving systemic health. Here we give an overview of the molecular factors that contribute to lifespan and healthspan, and discuss the effects of the longevity gene Cisd2 and middle-to-old age exercise on muscle metabolism and changes in the muscle transcriptome in mice during very old age.

MeSH Terms

-

Keywords

Cisd2; aging; exercise; metabolism; skeletal muscle

Cellular proteostasis decline in human senescence.

Abstract

Proteostasis collapse, the diminished ability to maintain protein homeostasis, has been established as a hallmark of nematode aging. However, whether proteostasis collapse occurs in humans has remained unclear. Here, we demonstrate that proteostasis decline is intrinsic to human senescence. Using transcriptome-wide characterization of gene expression, splicing, and translation, we found a significant deterioration in the transcriptional activation of the heat shock response in stressed senescent cells. Furthermore, phosphorylated HSF1 nuclear localization and distribution were impaired in senescence. Interestingly, alternative splicing regulation was also dampened. Surprisingly, we found a decoupling between different unfolded protein response (UPR) branches in stressed senescent cells. While young cells initiated UPR-related translational and transcriptional regulatory responses, senescent cells showed enhanced translational regulation and endoplasmic reticulum (ER) stress sensing; however, they were unable to trigger UPR-related transcriptional responses. This was accompanied by diminished ATF6 nuclear localization in stressed senescent cells. Finally, we found that proteasome function was impaired following heat stress in senescent cells, and did not recover upon return to normal temperature. Together, our data unraveled a deterioration in the ability to mount dynamic stress transcriptional programs upon human senescence with broad implications on proteostasis control and connected proteostasis decline to human aging.

MeSH Terms

-

Keywords

UPR; chaperones; heat shock response; protein homeostasis; senescence

The Neural Correlates of Visual and Auditory Cross-Modal Selective Attention in Aging.

Abstract

Age-related deficits in selective attention have been demonstrated to depend on the sensory modality through which targets and distractors are presented. Some of these investigations suggest a specific impairment of cross-modal auditory selective attention. For the first time, this study is taking on a whole brain approach while including a passive perception baseline, to investigate the neural underpinnings of selective attention across age groups, and taking the sensory modality of relevant and irrelevant (i.e., distracting) stimuli into account. Sixteen younger (mean age = 23.3 years) and 14 older (mean age = 65.3 years), healthy participants performed a series of delayed match-to-sample tasks, in which participants had to selectively attend to visual stimuli, selectively attend to auditory stimuli, or passively view and hear both types of stimuli, while undergoing 3T fMRI. The imaging analyses showed that areas recruited by cross-modal visual and auditory selective attention in both age groups included parts of the dorsal attention and frontoparietal control networks (i.e., intraparietal sulcus, insula, fusiform gyrus, anterior cingulate, and inferior frontal cortex). Most importantly, activation throughout the brain did not differ across age groups, suggesting intact brain function during cross-modal selective attention in older adults. Moreover, stronger brain activation during cross-modal visual vs. cross-modal auditory selective attention was found in both age groups, which is consistent with earlier accounts of visual dominance. In conclusion, these results do not support the hypothesized age-related deficit of cross-modal auditory selective attention. Instead, they suggest that the underlying neural correlates of cross-modal selective attention are similar in younger and older adults.

MeSH Terms

-

Keywords

aging; selective attention; sensory modality; top-down modulation; whole-brain fMRI

Audio-Visual Training in Older Adults: 2-Interval-Forced Choice Task Improves Performance.

Abstract

A growing interest in ameliorating multisensory perception deficits in older adults arises from recent evidence showing that impaired multisensory processing, particularly in the temporal domain, may be associated with cognitive and functional impairments. Perceptual training has proved successful in improving multisensory temporal processing in young adults, but few studies have investigated this training approach in older adults. In the present study we used a simultaneity (or synchronicity) judgement task with feedback, to train the audio-visual abilities of community-dwelling, cognitively healthy older adults. We recruited 23 older adults ([i]M[/i] = 74.17, [i]SD[/i] = 6.23) and a group of 20 young adults ([i]M[/i] = 24.20, [i]SD[/i] = 4.23) who served as a comparison. Participants were tested before and after perceptual training using a 2-Interval Forced Choice Task (2-IFC); and the Sound-Induced Flash Illusion (SIFI). After 3 days of training, participants improved on the 2-IFC task, with a significant narrowing of the temporal window of integration (TWI) found for both groups. Generalization of training effects was not found, with no post-training differences in perceptual sensitivity to the SIFI for either group. These findings provide evidence perceptual narrowing can be achieved in older as well as younger adults after 3 days of perceptual training. These results provide useful information for future studies attempting to improve audio-visual temporal discrimination abilities in older people.

MeSH Terms

-

Keywords

aging; audio-visual; multisensory; perceptual learning; sound-induced flash illusion; training

Thermal Aging Rheological Behavior of Magnetorheological Elastomers Based on Silicone Rubber.

Abstract

Engineering rubber composites have been widely used as main components in many fields including vehicle engineering and biomedical applications. However, when a rubber composite surface area is exposed to heat or sunlight and over a long-term accelerated exposure and lifecycle of test, the rubber becomes hard, thus influencing the mechanical and rheological behavior of the materials. Therefore, in this study, the deterioration of rheological characteristics particularly the phase shift angle (δ) of silicone rubber (SR) based magnetorheological elastomer (MRE) is investigated under the effect of thermal aging. SR-MRE with 60 wt% of CIPs is fabricated and subjected to a continuous temperature of 100 °C for 72 h. The characterization of SR-MRE before and after thermal aging related to hardness, micrograph, and rheological properties are characterized using low vacuum scanning electron microscopy (LV-SEM) and a rheometer, respectively. The results demonstrated that the morphological analysis has a rough surface and more voids occurred after the thermal aging. The hardness and the weight of the SR-MRE before and after thermal aging were slightly different. Nonetheless, the thermo-rheological results showed that the stress-strain behavior have changed the phase-shift angle (δ) of SR-MRE particularly at a high strain. Moreover, the complex mechanism of SR-MRE before and after thermal aging can be observed through the changes of the 'in-rubber structure' under rheological properties. Finally, the relationship between the phase-shift angle (δ) and the in-rubber structure due to thermal aging are discussed thoroughly which led to a better understanding of the thermo-rheological behavior of SR-MRE.

MeSH Terms

-

Keywords

Payne effect; magnetorheological elastomer; phase shift angle; rheological properties; thermal aging; thermo-rheological

Influence of [i]BDNF[/i] Genetic Polymorphisms in the Pathophysiology of Aging-related Diseases.

Abstract

For the first time in history, most of the population has a life expectancy equal or greater than 60 years. By the year 2050, it is expected that the world population in that age range will reach 2000 million, an increase of 900 million with respect to 2015, which poses new challenges for health systems. In this way, it is relevant to analyze the most common diseases associated with the aging process, namely Alzheimer´s disease, Parkinson Disease and Type II Diabetes, some of which may have a common genetic component that can be detected before manifesting, in order to delay their progress. Genetic inheritance and epigenetics are factors that could be linked in the development of these pathologies. Some researchers indicate that the [i]BDNF[/i] gene is a common factor of these diseases, and apparently some of its polymorphisms favor the progression of them. In this regard, alterations in the level of BDNF expression and secretion, due to polymorphisms, could be linked to the development and/or progression of neurodegenerative and metabolic disorders. In this review we will deepen on the different polymorphisms in the [i]BDNF[/i] gene and their possible association with age-related pathologies, to open the possibilities of potential therapeutic targets.

MeSH Terms

-

Keywords

Aging; BDNF gene; aging-related diseases; polymorphism

Physical and Behavioral Health Characteristics of Aging Homeless Women in the United States: An Integrative Review.

Abstract

The average age of the homeless population is and will continue to rise. Although women comprise a significant and growing percentage of this vulnerable population, their age- and sex-specific health characteristics are poorly understood.   This integrative review appraises published research addressing the physical and behavioral health characteristics of aging homeless women (≥50 years) in the United States (2000-2019). The authors searched six electronic databases to identify eligible studies. Studies were screened for methodological quality by using the Johns Hopkins Nursing Evidence-Based Practice model. The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.   Ten primary studies met the review eligibility criteria. All were level III (non-experimental); nine appraised as "good" quality (level B), and one as "lower" quality (level C). Aging homeless women demonstrate elevated rates of physical health conditions, related to suboptimal nutrition, lower than expected preventive health screening uptake, and geriatric concerns. Disproportionate rates of mental health conditions are compounded by substance use and interpersonal trauma. Familial and social dynamics and socioeconomic disadvantage contribute to social health concerns. Spiritual health is a critically important yet underexplored protective factor.   Studies are limited, though collective findings suggest that aging homeless women endure a disproportionate physical, behavioral, and social health burden compared with aging non-homeless women and aging homeless men. Implications for research on early aging, preventative health strategies, and homelessness among women, and clinical practice in the context of geriatric and women's health are described.

MeSH Terms

-

Keywords

aging; health disparities; homelessness; older adult; women's health

Reading the Mind in the Eyes: A Population-Based Study of Social Cognition in Older Adults.

Abstract

Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. Although it is one of the six core DSM-5 cognitive domains for diagnosing neurocognitive disorders, it is not routinely assessed in older adults. The Reading the Mind in the Eyes Test assesses Theory of Mind, the social cognition mechanism which forms the root of empathy. To describe the distribution of, and factors associated with, scores on a 10-item version of Reading the Mind in the Eyes Test (RMET-10) in older adults. Population-based cross-sectional study. Small-town communities in Pennsylvania. Adults aged 66-105 years (N = 902, mean age = 76.6). The assessment included RMET-10, demographics, cognitive screening, literacy, depression symptoms, anxiety symptoms, cognitive composites derived from a neuropsychological test battery, Social Norms Questionnaire, and Clinical Dementia Rating (CDR). RMET-10 score was normally distributed in our overall study sample. Normative RMET-10 scores among those rated as CDR = 0 were calculated by age, sex, and education. RMET-10 score was significantly higher with younger age, higher education, white race, higher cognitive screening scores, literacy, social norms scores, higher scores in all five domains in cognitive composites, and lower CDR. RMET-10 score was also significantly higher with fewer depression and anxiety symptoms after adjusting for demographics. The RMET is a potentially useful measure of social cognition for use in the research assessment of older adults. With appropriate calibration it should also have utility in the clinical setting.

MeSH Terms

-

Keywords

Aging; Reading the Mind in the Eyes Test (RMET); cognitive empathy; community-based; epidemiology; theory of mind

Strategies to Prevent Serious Fall Injuries: A Commentary on Bhasin et al. A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries. [i]N Engl J Med[/i]. 2020;383(2):129-140.

Abstract

Every second of every day, an older adult suffers a fall in the United States (>30 million older adults fall each year). More than 20% of these falls cause serious injury (e.g., broken bones, head injury) and result in 800,000 hospitalizations and 30,000 deaths annually. Bhasin and colleagues recently reported results from a pragmatic, cluster-randomized trial designed to evaluate the effectiveness of a multifactorial intervention to prevent fall injuries. The intervention did not result in a significantly lower rate of a first adjudicated serious fall injury among older adults at increased risk for fall injuries as compared with enhanced usual care. In this commentary we briefly review and highlight these recent findings. Additionally, we argue that the findings should not be discounted just because of the lack of statistical significance. The approximately 10% reduction compared to enhanced usual care is, arguably, meaningful at both the individual and public health level, especially when one considers that the control group had better outcomes than expected based on prior work. Moreover, we encourage future research as well as practitioners to give strong consideration to the nuances of the exercise interventions for reducing falls and fall-related injuries particularly as it relates to exercise programming specifics, namely intensity and volume, to enhance neuromuscular function and also to neurorehabilitation approaches to enhance motor function (e.g., balance, motor planning, and coordination).

MeSH Terms

-

Keywords

aging; fractures; frailty; mobility

Does dance counteract age-related cognitive and brain declines in middle-aged and older adults? A systematic review.

Abstract

Dance is a multidomain activity that combines aerobic, coordination and cognitive exercise. This music-associated physical and cognitive exercise is a leisure activity that motivates people, elicits emotions, and avoids boredom, promoting adherence to practice. Continuing physical activity is of paramount importance, since cognitive benefits tend to disappear or even reverse when training ceases. The question we addressed in this systematic review is what influence dance has on the brain and cognition of healthy middle-aged and older adults. We systematically reviewed the effects of dance on brain and cognition in older adults using MEDLINE, Psyc-Info, PubMed and Scopus databases. After screening 1,051 studies, thirty-five met the eligibility inclusion criteria. These studies showed that dance improves brain structure and function as well as physical and cognitive functions. The protective effect of dance training on cognition in older adults, together with the possibility of adapting intensity and style to suit possible physical limitations makes this activity very suitable for older adults.

MeSH Terms

-

Keywords

Aging; dance; music; neuroplasticity; physical exercise

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells.

Abstract

The Chinese herbal formula Heshouwu decoction (Heshouwuyin) has protective effects on testicular function in aging male rats, but the mechanism is unknown. This study investigated whether Heshouwuyin affects the testicular function of aging rats by regulating the insulin/IGF signalling pathway. Sixteen-month-old male Wistar rats in the Heshouwuyin group and the natural-aging group were orally administered Heshouwuyin granules (0.056 g/kg) or equivalent normal saline for 60 d. The testicular tissue of 12-month-old male Wistar rats was removed as a young control group ([i]n[/i] = 10). The testicular tissue and spermatogenic cells were studied. The immunofluorescence results revealed that the insulin receptor (INSR)- (0.056 ± 0.00548), insulin receptor substrate 1(IRS1)- (0.251 ± 0.031), IRS2 (0.230 ± 0.019)- and insulin-like growth factor 1 (IGF1)-positive cell rate (0.33 ± 0.04) in the aging group was higher than that in the young control group (0.116 ± 0.011, 0.401 ± 0.0256, 0.427 ± 0.031, 0.56 ± 0.031; [i]p[/i] < 0.01), and the IGF-binding protein 3 (IGFBP3)-positive cell rate (0.42 ± 0.024) was lower than that (0.06 ± 0.027) in the young group ([i]p[/i] < 0.01). The intervention of Heshouwuyin reversed the above phenomena. The qPCR and immunoblot results were consistent with those of the immunofluorescence. The same results were obtained in spermatogenic cells. Our research shows that Heshouwuyin can regulate the insulin/IGF signalling pathway to improve testicular function, and provides an experimental basis for further clinical use.

MeSH Terms

-

Keywords

IGF1; IGFBP3; INSR; IRS1; IRS2; Male reproduction; senescence

SOD1, more than just an antioxidant.

Abstract

During cellular respiration, radicals, such as superoxide, are produced, and in a large concentration, they may cause cell damage. To combat this threat, the cell employs the enzyme Cu/Zn Superoxide Dismutase (SOD1), which converts the radical superoxide into molecular oxygen and hydrogen peroxide, through redox reactions. Although this is its main function, recent studies have shown that the SOD1 has other functions that deviates from its original one including activation of nuclear gene transcription or as an RNA binding protein. This comprehensive review looks at the most important aspects of human SOD1 (hSOD1), including the structure, properties, and characteristics as well as transcriptional and post-translational modifications (PTM) that the enzyme can receive and their effects, and its many functions. We also discuss the strategies currently used to analyze it to better understand its participation in diseases linked to hSOD1 including Amyotrophic Lateral Sclerosis (ALS), cancer, and Parkinson.

MeSH Terms

-

Keywords

Aging; Cancer; Neurodegenerative diseases; Post-translational modifications; Superoxide dismutase 1

Caregiver Well-Being and Burden: Variations by Race/Ethnicity and Care Recipient Nativity Status.

Abstract

Despite growing diversity among the aging population and extensive previous research on racial/ethnic minority caregivers, little research has been conducted on the potentially unique experiences and outcomes of informal caregivers of foreign-born care recipients. Using nationally representative data and the Stress Process Model, the current study examined the differences in caregiver outcomes (care burden, psychological well-being, and self-rated health) by care recipient nativity status (U.S.-born vs. foreign-born) and the extent to which caregiver outcomes vary by care recipient nativity status and caregiver race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and Others). The current study used Round 5 of the National Health and Aging Trends Study and the National Study of Caregiving ([i]N[/i] = 1,436). We conducted ordinary least squares regression to analyze the differences in caregiver's outcomes by care recipient nativity status and caregiver race/ethnicity and to investigate the impacts of the inclusion of caregiving factors (background factors, primary stressors, secondary stressors, and resources). Regression analyses showed that only care burden significantly varied by care recipient nativity status after controlling for covariates. Caregivers of foreign-born care recipients reported a higher burden. However, when interactions of care recipient nativity status × caregiver race/ethnicity were introduced, non-Hispanic black and Hispanic caregivers of foreign-born care recipients were more likely to report better psychological well-being and self-rated health compared to their counterparts. Across caregiver groups, better caregiver-care recipient relationship quality and less caregiver chronic conditions were associated with less burden and better caregiver psychological well-being and self-rated health. Care recipient nativity status and caregiver race/ethnicity may have complex effects on caregiving experiences. Given the observed significant interaction effects for caregiver psychological well-being and self-rated health, cultural factors may affect the extent to which these caregivers appraise their caregiving. Future research should delve into the appropriate ways to assess care stress as well as resilience among each caregiver group. Our results indicate the need for research, education, and practice that assess cultural and within-group differences among caregivers and inform needed changes to structural barriers.

MeSH Terms

-

Keywords

Caregivers; National Health and Aging Trends Study (NHATS) and the National Study of Caregiving (NSOC); Nativity status; Race/ethnicity

Age-related alterations of default mode network in autobiographical memory: Recent versus remote events.

Abstract

Previous studies have shown that the vividness of autobiographical memory decreases over time, and older adults often retrieve fewer details than young adults. However, the age-by-temporal distance (i.e., recent versus remote events) effect on autobiographical memory and underlying neural mechanisms are less understood. We recruited 25 young adults and 27 older adults to perform an fMRI-adapted autobiographical memory task with different temporal distances. The results showed that older adults' vividness ratings were generally higher than that of young adults, but were less sensitive to temporal distances. For neural imaging, an age-by-temporal distance effect was found in the left precuneus, manifested as young adults had more activation for recent events than for remote events, whereas no temporal distance effect was found in older adults. Interestingly, for older adults, the temporal distance effect was reflected by functional connectivity within the default mode network (DMN), with a stronger anterior DMN-posterior DMN coupling for remote events than for recent events, whereas no temporal distance difference on functional connectivity was found in young adults. The results suggest that older adults exhibit age-related neural differences in both activation and functional connectivity during the processing of autobiographical memory with different temporal distances, shedding new light for the understanding of the relationship between the DMN, autobiographical memory, and aging.

MeSH Terms

-

Keywords

aging; autobiographical memory; default mode network; functional connectivity; temporal distance

A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Aging is the most significant risk factor for late-onset AD. The age-associated changes in the immune system are termed immunosenescence. A close connection between immunosenescence and AD is increasingly recognized. This article provides an overview of immunosenescence and evidence for its role in the pathogenesis of AD and possible mechanisms as well as the outlook for drug development.

MeSH Terms

-

Keywords

Alzheimer’s disease; aging; immunosenescence; inflammation

The NPR1-WRKY46-WRKY6 signaling cascade mediates probenazole/salicylic acid-elicited leaf senescence in Arabidopsis thaliana.

Abstract

Endogenous salicylic acid (SA) regulates leaf senescence, but the underlying mechanism remains largely unexplored. The exogenous application of SA to living plants is not efficient for inducing leaf senescence. By taking advantage of probenazole (PBZ)-induced biosynthesis of endogenous SA, we previously established a chemical inducible leaf senescence system that depends on SA biosynthesis and its core signaling receptor NPR1 in Arabidopsis thaliana. Here, using this system, we identified WRKY46 and WRKY6 as key components of the transcriptional machinery downstream of NPR1 signaling. Upon PBZ treatment, the wrky46 mutant exhibited significantly delayed leaf senescence. We demonstrate that NPR1 is essential for PBZ/SA-induced WRKY46 activation, whereas WRKY46 in turn enhances NPR1 expression. WRKY46 interacts with NPR1 in the nucleus, binding to the W-box of the WRKY6 promoter to induce its expression in response to SA signaling. Dysfunction of WRKY6 abolished PBZ-induced leaf senescence, while overexpression of WRKY6 was sufficient to accelerate leaf senescence even under normal growth conditions, suggesting that WRKY6 may serve as an integration node of multiple leaf senescence signaling pathways. Taken together, these findings reveal that the NPR1-WRKY46-WRKY6 signaling cascade plays a critical role in PBZ/SA-mediated leaf senescence in Arabidopsis. This article is protected by copyright. All rights reserved.

MeSH Terms

-

Keywords

Leaf senescence; NPR1; Probenazole; Salicylic acid; WRKY46; WRKY6

The relationship of existential well - being to identity, religious coping, mental and general health among Norwegian aging women.

Abstract

The aim of this study was to explore the relationship of existential spirituality to identity processing, religious coping and mental and general health among younger and older aged women in Norway. Participant's included 120 women aged 31-91 who took part in a postal survey. Results showed that both accommodative and balancing identity processes were associated with existential well -being among both the younger and older aged. Among the younger - aged, mental health was also significantly associated with existential well-being, Moreover, among the older aged, religious coping in the form of discontent, was found to be associated with existential well-being.

MeSH Terms

-

Keywords

Identity; aging; women

Cyclic Ion Mobility Spectrometry Coupled to High-Resolution Time-of-Flight Mass Spectrometry Equipped with Atmospheric Solid Analysis Probe for the Molecular Characterization of Combustion Particulate Matter.

Abstract

Anthropogenic air pollution has a severe impact on climate and human health. The immense molecular complexity and diversity of particulate matter (PM) is a result of primary organic aerosol (POA) as well as secondary organic aerosols (SOAs). In this study, a direct inlet probe (DIP), i.e., atmospheric solids analysis probe (ASAP), with ion mobility high-resolution mass spectrometric detection is applied. Primary particulate matter emissions from three sources were investigated. Furthermore, photochemically aged emissions were analyzed. DIP introduction allowed for a direct analysis with almost no sample preparation and resulted in a complex molecular pattern. This pattern shifted through oxidation processes toward heavier species. For diesel emissions, the fuel's chemical characteristic is partially transferred to the particulate matter by incomplete combustion and characteristic alkylated series were found. Polycyclic aromatic hydrocarbons (PAHs) were identified as major contributors. Ion mobility analysis results in drift time profiles used for structural analysis. The apex position was used to prove structural changes, whereas the full-width-at-half-maximum was used to address the isomeric diversity. With this concept, the dominance of one or a few isomers for certain PAHs could be shown. In contrast, a broad isomeric diversity was found for oxygenated species. For the in-depth specification of fresh and aged spruce emissions, the ion mobility resolving power was almost doubled by allowing for three passes in the circular traveling wave design. The results prove that ASAP coupled with ion mobility spectrometry-mass spectrometry (IMS-MS) serves as a promising analytical approach for tackling the vast molecular complexity of PM.

MeSH Terms

-

Keywords

combustion emission; complex mixtures; cyclic ion mobility spectrometry; direct inlet probe; high-resolution mass spectrometry; particulate matter (PM); photochemical aerosol aging

Neuroimmunomodulation by estrogen in health and disease.

Abstract

Systemic homeostasis is maintained by the robust bidirectional regulation of the neuroendocrine-immune network by the active involvement of neural, endocrine and immune mediators. Throughout female reproductive life, gonadal hormones undergo cyclic variations and mediate concomitant modulations of the neuroendocrine-immune network. Dysregulation of the neuroendocrine-immune network occurs during aging as a cumulative effect of declining neural, endocrine and immune functions and loss of compensatory mechanisms including antioxidant enzymes, growth factors and co-factors. This leads to disruption of homeostasis and sets the stage for the development of female-specific age-associated diseases such as autoimmunity, osteoporosis, cardiovascular diseases and hormone-dependent cancers. Ovarian hormones especially estrogen, play a key role in the maintenance of health and homeostasis by modulating the nervous, endocrine and immune functions and thereby altering neuroendocrine-immune homeostasis. Immunologically estrogen's role in the modulation of Th1/Th2 immune functions and contributing to pro-inflammatory conditions and autoimmunity has been widely studied. Centrally, hypothalamic and pituitary hormones influence gonadal hormone secretion in murine models during onset of estrous cycles and are implicated in reproductive aging-associated acyclicity. Loss of estrogen affects neuronal plasticity and the ensuing decline in cognitive functions during reproductive aging in females implicates estrogen in the incidence and progression of neurodegenerative diseases. Peripherally, sympathetic noradrenergic (NA) innervations of lymphoid organs and the presence of both adrenergic (AR) and estrogen receptors (ER) on lymphocytes poise estrogen as a potent neuroimmunomodulator during health and disease. Cyclic variations in estrogen levels throughout reproductive life, perimenopausal surge in estrogen levels followed by its precipitous decline, concomitant with decline in central hypothalamic catecholaminergic activity, peripheral sympathetic NA innervation and associated immunosuppression present an interesting study to explore female-specific age-associated diseases in a new light.

MeSH Terms

-

Keywords

17 β-estradiol; autoimmunity; immunosenescence; neural-immune; neuroendocrine; norepinephrine; reproductive aging

Exploring rural older adult perspectives on the scope, reach and sustainability of age-friendly programs.

Abstract

Research into the sustainability of age-friendly initiatives is important and timely, particularly from the rather neglected perspective of older adults living in non-metropolitan (rural) environments. This paper addresses this gap by reporting on a Canadian rural community case study to understand the perspectives of older adults on the implementation and sustainability of their local age-friendly program. Findings from exploratory interviews with 10 older adults suggest that rural age-friendly initiatives may be limited in their ability to achieve larger-scale outcomes aimed at addressing broad aging issues facing rural communities. Further, our findings demonstrate that those 'aging in place' may continue to do so with the support of age-friendly programing, while those 'stuck in place' are largely unaffected by age-friendly programs. We advocate for additional in-depth examinations of rural age-friendly sustainability, including a greater emphasis on the diversity of older adult perspectives.

MeSH Terms

-

Keywords

Age-friendly communities; Implementation; Older adults; Rural aging; Sustainability

Long-term sustainable phosphorus (P) retention in a low-P stormwater wetland for Everglades restoration.

Abstract

The Stormwater Treatment Areas (STAs) are large wetlands constructed for phosphorus (P) retention for Everglades restoration in south Florida (USA), and include areas of submerged aquatic vegetation (SAV) at a globally unprecedented scale (~12,000 ha). The goal of this study was to elucidate the fate of P retained in large-scale SAV wetlands, and the associated temporal trends in P removal and retention. In a well-performing, 929-ha SAV-dominated STA surface water flow-through treatment wetland, measurements of accrued soil depth and soil P storage performed every ~4-6 years revealed a steady-state longitudinal soil P enrichment profile established within the first ~4 years of flow-through operation. Subsequently, the SAV soils accrued P at a relatively steady rate (1.13 g P m  yr for the entire 17-year period) without indication of temporal P enrichment, spatial expansion of soil P enrichment in the inflow region, or impairment of water column P removal efficiency. Phosphorus sequestration occurred via accumulation of new sedimentary material (0.9-1.5 cm yr ), rather than enrichment of existing soil. These soil surveys were accompanied by measurements of porewater SRP concentrations, soil P release under anoxia, and soil P fractions, which demonstrated that soil P release potential and concentrations of highly labile soil P generally decreased over time. These findings demonstrate that the P retention mechanisms operating within this large SAV wetland can be sustainable under managed steady-state conditions. Susceptibility of SAV to extreme environmental perturbations in this and other wetlands, however, remains a research priority.

MeSH Terms

-

Keywords

Longevity; P saturation; SAV wetlands; Soil accretion; Steady state

Stimulation of epidermal hyperplasia and tumorigenesis by resident p16 -expressing cells.

Abstract

p16 (CDKN2A) is a central tumor-suppressor and activator of senescence. We recently found that prolonged expression of p16 in epidermal cells induces hyperplasia and dysplasia through Wnt-mediated stimulation of neighboring keratinocytes. The study suggests a pro-tumorigenic function of p16 in early epidermal lesions, which could potentially be targeted by senolytic therapy.

MeSH Terms

-

Keywords

CDKN2A; P16ink4a; Wnt; aging; epidermis; senescence

Age Patterning in Wild Chimpanzee Gut Microbiota Diversity Reveals Differences from Humans in Early Life.

Abstract

Survival in primates is facilitated by commensal gut microbes that ferment otherwise indigestible plant matter, resist colonization by pathogens, and train the developing immune system. However, humans are unique among primates in that we consume highly digestible foods, wean early, mature slowly, and exhibit high lifelong investments in maintenance. These adaptations suggest that lifetime trajectories of human-microbial relationships could differ from those of our closest living relatives. Here, we profile the gut microbiota of 166 wild chimpanzees aged 8 months to 67 years in the Kibale National Park, Uganda and compare the patterns of gut microbial maturation to those previously observed in humans. We found that chimpanzee gut microbial alpha-diversity, composition, density, interindividual variation, and within-individual change over time varied significantly with age. Notably, gut microbial signatures in infants <2 years old were distinct across all five metrics. Infant chimpanzee guts were enriched in some of the same taxa prevalent in infant humans (e.g., Bifidobacterium, Streptococcus, and Bacteroides), and chimpanzee gut microbial communities, like those of humans, exhibited higher interindividual variation in infancy versus later in life. However, in direct contrast to human infants, chimpanzee infants harbored surprisingly high-diversity rather than low-diversity gut bacterial communities compared with older conspecifics. These data indicate differential trajectories of gut microbiota development in humans and chimpanzees that are consistent with interspecific differences in lactation, diet, and immune function. Probing the phenotypic consequences of differential early-life gut microbial diversity in chimpanzees and other primates will illuminate the life history impacts of the hominid-microbiome partnership.

MeSH Terms

-

Keywords

aging; chimpanzee; development; diversity; gut microbiota; infancy; maturation; microbiome; primate; weaning

Sex differences in risk factors for white matter hyperintensities in non-demented older individuals.

Abstract

White matter hyperintensities (WMH) are generally considered to be associated with cerebral small vessel disease, especially, in older age. Although significant sex differences have been reported in the severity of WMH, it is not yet known if the risk factors for WMH differ in men and women. In this study, magnetic resonance imaging brain scans from 2 Australian cohorts were analyzed to extract WMH volumes. The objective of this study is to examine the moderation effect by sex in the association between known risk factors and WMH. The burden of WMH was significantly higher in women compared to men, especially in the deep WMH (DWMH). In the generalized linear model that included the interaction between sex and body mass index (BMI), there was a differential association of BMI with DWMH in men and women in the exploratory sample, that is, the Sydney Memory and Aging Study, n = 432, aged between 70 and 90. The finding of a higher BMI associated with a higher DWMH in men compared to women was replicated in the Older Australian Twins Study sample, n = 179, aged between 65 and 90. The risk factors of WMH pathology are suggested to have a different impact on the aging brains of men and women.

MeSH Terms

-

Keywords

Aging; Body mass index (BMI); Cerebral small vessel disease; Neuroimaging; Obesity; Sex differences; White matter hyperintensity (WMH)

Prevention of Fine Dust-Induced Vascular Senescence by [i]Humulus lupulus[/i] Extract and Its Major Bioactive Compounds.

Abstract

Both short- and long-term exposure to fine dust (FD) from air pollution has been linked to various cardiovascular diseases (CVDs). Endothelial cell (EC) senescence is an important risk factor for CVDs, and recent evidence suggests that FD-induced premature EC senescence increases oxidative stress levels. Hop plant ([i]Humulus lupulus[/i]) is a very rich source of polyphenols known to have nutritional and therapeutic properties, including antioxidant behavior. The aims of this study were to evaluate whether [i]Humulus lupulus[/i] extract prevents FD-induced vascular senescence and dysfunction and, if so, to characterize the underlying mechanisms and active components. Porcine coronary arteries and endothelial cells were treated with FD in the presence or absence of hop extract (HOP), and the senescence-associated-beta galactosidase (SA-β-gal) activity, cell-cycle progression, expression of senescence markers, oxidative stress level, and vascular function were evaluated. Results indicated that HOP inhibited FD-induced SA-β-gal activity, cell-cycle arrest, and oxidative stress, suggesting that HOP prevents premature induction of senescence by FD. HOP also ameliorated FD-induced vascular dysfunction. Additionally, xanthohumol (XN) and isoxanthohumol (IX) were found to produce the protective effects of HOP. Treatment with HOP and its primary active components XN and IX downregulated the expression of p22 , p53, and angiotensin type 1 receptor, which all are known FD-induced redox-sensitive EC senescence inducers. Taken together, HOP and its active components protect against FD-induced endothelial senescence most likely via antioxidant activity and may be a potential therapeutic agent for preventing and/or treating air-pollution-associated CVDs.

MeSH Terms

-

Keywords

Humulus lupulus; air pollution; endothelial dysfunction; endothelial senescence; fine dust; isoxanthohumol; oxidative stress; xanthohumol

An Information Theory Approach for the Analysis of Individual and Combined Evaluation Parameters of Multiple Age-Related Diseases.

Abstract

In view of the frequent presence of several aging-related diseases in geriatric patients, there is a need to develop analytical methodologies that would be able to perform diagnostic evaluation of several diseases at once by individual or combined evaluation parameters and select the most informative parameters or parameter combinations. So far there have been no established formal methods to enable such capabilities. We develop a new formal method for the evaluation of multiple age-related diseases by calculating the informative values (normalized mutual information) of particular parameters or parameter combinations on particular diseases, and then combine the ranks of informative values to provide an overall estimation (or correlation) on several diseases at once. Using this methodology, we evaluate a geriatric cohort, with several common age-related diseases, including cognitive and physical impairments (dementia, chronic obstructive pulmonary disease-COPD and ischemic heart disease), utilizing a set of evaluation parameters (such as demographic data and blood biomarkers) routinely available in geriatric clinical practice. This method permitted us to establish the most informative parameters and parameter combinations for several diseases at once. Combinations of evaluation parameters were shown to be more informative than individual parameters. This method, with additional clinical data, may help establish the most informative parameters and parameter combinations for the diagnostic evaluation of multiple age-related diseases and enhance specific assessment for older multi-morbid patients and treatments against old-age multimorbidity.

MeSH Terms

-

Keywords

aging; aging-related diseases; information theory; multimorbidity; normalized mutual information

Case Series and Review of Hematological and Non-Hematological Malignancies in Aging Patients with Sickle Cell Disease in the Hydroxyurea Era.

Abstract

Survival of adult patients with sickle cell disease has increased progressively since the 1970s. Aging patients with sickle cell disease are at risk of developing comorbidities that are not due to sickle cell disease itself, including malignancies. Many studies tried to assess the incidence of malignancy in patients with sickle cell disease. However, no studies have been done to evaluate cancer incidences in aging sickle cell patients, especially in the hydroxyurea (HU) era. In this review, we assessed the prevalence of malignancies in aging patients with sickle cell disease at our institution with or without HU therapy. Retrospective analysis of hospital records identified patients who had been diagnosed to carry sickle cell disease and malignancies before 2020 using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding. Four hundred and eighty-three sickle cell disease patients were seen in our inpatients/outpatients offices. Among these, 12 sickle cell disease patients had a confirmed diagnosis of malignancy. The patients were classified into three categories based on age groups: four patients who were 60 years and older had multiple myeloma. Solid tumors were found in 5/6 patients, aged 40-60 who had the Hb S ([i]HBB[/i]: c.20A>T) (β /β ) genotype with signs of iron overload. Two patients, aged 25 and 35, had hematological malignancies. The number of patients on HU was too small to make any comment on relationship to malignancy or mortality. This study is only one institution's experience, further investigation on a larger scale is needed to look into cancer incidences in this population.

MeSH Terms

-

Keywords

Aging sickle cell patients; hydroxyurea (HU); malignancies

Hyaluronan degradation and release of a hyaluronan-aggrecan complex from perineuronal nets in the aged mouse brain.

Abstract

Perineuronal nets (PNNs) are insoluble aggregates of extracellular matrix molecules in the brain that consist of hyaluronan (HA) and chondroitin sulfate proteoglycans (CSPGs). PNNs promote the acquisition and storage of memories by stabilizing the formation of synapses in the adult brain. Although the deterioration of PNNs has been suggested to contribute to the age-dependent decline in brain function, the molecular mechanisms underlying age-related changes in PNNs remain unclear. The amount and solubility of PNN components were investigated by sequential extraction followed by a disaccharide analysis and immunoblotting. We examined the interaction between HA and aggrecan, a major HA-binding CSPG, by combining mass spectrometry and pull-down assays. The solubility and amount of HA increased in the brain with age. Among several CSPGs, the solubility of aggrecan was selectively elevated during aging. In contrast to alternations in biochemical properties, the expression of PNN components at the transcript level was not markedly changed by aging. The increased solubility of aggrecan was not due to the loss of HA-binding properties. Our results indicated that the degradation of high-molecular-mass HA induced the release of the HA-aggrecan complex from PNNs in the aged brain. The present study revealed a novel mechanism underlying the age-related deterioration of PNNs in the brain.

MeSH Terms

-

Keywords

Brain aging; Chondroitin sulfate proteoglycan; Extracellular matrix; Hyaluronan; Perineuronal net

Increased Social Interactions Reduce the Association Between Constricted Life-Space and Lower Daily Happiness in Older Adults With and Without HIV: A GPS and Ecological Momentary Assessment Study.

Abstract

Older persons with human immunodeficiency virus (HIV) (PWH) are particularly susceptible to life-space restrictions. The aims of this study included: 1) using global positioning system (GPS) derived indicators as an assessment of time spent at home among older adults with and without HIV; 2) using ecological momentary assessment (EMA) to examine real-time relationships between life-space, mood (happiness, sadness, anxious), fatigue, and pain; and 3) determining if number of daily social interactions moderated the effect of life-space on mood. Eighty-eight older adults (PWH n = 54, HIV-negative n = 34) completed smartphone-based EMA surveys assessing mood, fatigue, pain, and social interactions four times per day for two weeks. Participants' smartphones were GPS enabled throughout the study. Mixed-effects regression models analyzed concurrent and lagged associations among life-space and behavioral indicators of health. PWH spent more of their time at home (79% versus 70%, z = -2.08; p = 0.04) and reported lower mean happiness (3.2 versus 3.7; z = 2.63; p = 0.007) compared to HIV-negative participants. Controlling for covariates, more daily social interactions were associated with higher ratings of real-time happiness (b = 0.12; t = 5.61; df = 1087.9; p< 0.001). Similar findings were seen in lagged analyses: prior day social interactions (b = 0.15; t = 7.3; df = 1024.9; p < 0.0001) and HIV status (b = -0.48; t = -2.56; df = 1026.8; p = 0.01) attenuated the effect of prior day time spent at home on happiness. Accounting for engagement in social interactions reduced the significant effect of time spent at home and lower happiness. Interventions targeting social isolation within the context of constricted life-space may be beneficial for increasing positive mood in older adults, and especially relevant to older PWH.

MeSH Terms

-

Keywords

Remote assessment; aging; isolation; mobile health; mood; well-being

Black-white disparities during an epidemic: Life expectancy and lifespan disparity in the US, 1980-2000.

Abstract

Covid-19 has demonstrated again that epidemics can affect minorities more than the population in general. We consider one of the last major epidemics in the United States: HIV/AIDS from ca. 1980-2000. We calculate life expectancy and lifespan disparity (a measure of variance in age at death) for thirty US states, finding noticeable differences both between states and between the black and white communities. Lifespan disparity allows us to examine distributional effects, and, using decomposition methods, we find that for six states lifespan disparity for blacks increased between 1980 and 1990, while life expectancy increased less than for whites. We find that we can attribute most of this to the impact of HIV/AIDS.

MeSH Terms

-

Keywords

AIDS; HIV; Life expectancy; Lifespan disparity

Comparing the Effect of TGF-β Receptor Inhibition on Human Perivascular Mesenchymal Stromal Cells Derived from Endometrium, Bone Marrow and Adipose Tissues.

Abstract

Rare perivascular mesenchymal stromal cells (MSCs) with therapeutic properties have been identified in many tissues. Their rarity necessitates extensive in vitro expansion, resulting in spontaneous differentiation, cellular senescence and apoptosis, producing therapeutic products with variable quality and decreased potency. We previously demonstrated that A83-01, a transforming growth factor beta (TGF-β) receptor inhibitor, maintained clonogenicity and promoted the potency of culture-expanded premenopausal endometrial MSCs using functional assays and whole-transcriptome sequencing. Here, we compared the effects of A83-01 on MSCs derived from postmenopausal endometrium, menstrual blood, placenta decidua-basalis, bone marrow and adipose tissue. Sushi-domain-containing-2 (SUSD2 ) and CD34 CD31 CD45 MSCs were isolated. Expanded MSCs were cultured with or without A83-01 for 7 days and assessed for MSC properties. SUSD2 identified perivascular cells in the placental decidua-basalis, and their maternal origin was validated. A83-01 promoted MSC proliferation from all sources except bone marrow and only increased SUSD2 expression and prevented apoptosis in MSCs from endometrial-derived tissues. A83-01 only improved the cloning efficiency of postmenopausal endometrial MSCs (eMSCs), and expanded adipose tissue MSCs (adMSCs) underwent significant senescence, which was mitigated by A83-01. MSCs derived from bone marrow (bmMSCs) were highly apoptotic, but A83-01 was without effect. A83-01 maintained the function and phenotype in MSCs cultured from endometrial, but not other, tissues. Our results also demonstrated that cellular SUSD2 expression directly correlates with the functional phenotype.

MeSH Terms

-

Keywords

SUSD2; adipose tissue; apoptosis; bone marrow; clonogenicity; endometrium; menstrual fluid; perivascular mesenchymal stromal cells; placenta; senescence

Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin.

Abstract

Estrogen is a pivotal signaling molecule; its production is regulated by the expression of the aromatase (CYP19A1) gene from ovarian and peripheral tissue sites, and it is transmitted via estrogen receptors to influence many important biological functions. However, the narrative for this overview focuses on the decline of 17β-estradiol levels from ovarian sites after menopause. This estrogen-deficient condition is associated with a dramatic reduction in skin health and wellness by negatively impacting dermal cellular and homeostatic mechanisms, as well as other important biological functions. The changes include loss of collagen, elastin, fibroblast function, vascularity, and increased matrix metalloproteinase(s) enzymatic activities, resulting in cellular and extracellular degradation that leads to dryness, wrinkles, atrophy, impaired wound healing/barrier function, decreased antioxidant capacity [i.e., defense against reactive oxygen species (ROS) and oxidative stress], decreased attractiveness and psychological health, and increased perception of aging. While topical estrogen may reverse these changes, the effects of today's low-dose systemic hormone treatments are not well established, raising the need for more concentrated local administration of hormones or newer cosmeceutical agents such as selective estrogen receptor modulators (SERMs), including phytoestrogens that have become major active ingredients for skin care products, especially when addressing estrogen-deficient skin. Two example compounds are presented, an analog of resveratrol (i.e., 4'-acetoxy resveratrol) and the isoflavonoid equol, both of which are involved in a variety of biochemical/molecular actions and mechanisms, as demonstrated via in vitro and clinical studies that enhance human dermal health, especially in estrogen-deficient skin.

MeSH Terms

-

Keywords

4′-Acetoxy resveratrol; Aging; Cosmeceuticals; Equol; Estrogen; Estrogen deficient skin; Hormone therapy; Menopause; Polyphenols; Skin

A Blockchain-Based Consent Platform for Active Assisted Living: Modeling Study and Conceptual Framework.

Abstract

Recent advancements in active assisted living (AAL) technologies allow older adults to age well in place. However, sensing technologies increase the complexity of data collection points, making it difficult for users to consent to data collection. One possible solution for improving transparency in the consent management process is the use of blockchain, an immutable and timestamped ledger. This study aims to provide a conceptual framework based on technology aimed at mitigating trust issues in the consent management process. The consent management process was modeled using established methodologies to obtain a mapping of trust issues. This mapping was then used to develop a conceptual framework based on previous monitoring and surveillance architectures for connected devices. In this paper, we present a model that maps trust issues in the informed consent process; a conceptual framework capable of providing all the necessary underlining technologies, components, and functionalities required to develop applications capable of managing the process of informed consent for AAL, powered by blockchain technology to ensure transparency; and a diagram showing an instantiation of the framework with entities comprising the participants in the blockchain network, suggesting possible technologies that can be used. Our conceptual framework provides all the components and technologies that are required to enhance the informed consent process. Blockchain technology can help overcome several privacy challenges and mitigate trust issues that are currently present in the consent management process of data collection involving AAL technologies.

MeSH Terms

-

Keywords

Internet of Things; aging; blockchain; computer security; computing methodologies; health care; informed consent; mobile phone

An outpatient Tai Chi program: Effects on veterans' functional outcomes.

Abstract

To evaluate the effectiveness of an evidence-based 12-week Tai Chi course designed to improve balance and physical function in a population of older veterans. Community dwelling veterans of all ages with gait and balance problems were invited to participate in the Tai Chi program. Participants completed the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Falls Efficacy Scale-International (FES-I) at baseline and again at the end of the program. Descriptive statistics were used to summarize study participants' characteristics. The change from baseline to the end of the 12-week program was calculated for each of the three primary outcome variables (BBS, TUG, FES-I). Twenty-two veterans, aged 58 years and above, with perceived gait and/or balance issues were enrolled in the program with completion by 11 veterans. Veterans who completed their final assessments showed the BBS, improved significantly (p = 0.004) from baseline to the 12-week assessment. The TUG scores improved by a median of 1.3 s (p = 0.022). There was not a significant change in the FES-I. Preliminary findings provide evidence of the effectiveness of a 12-week Tai Chi program to improve functional outcomes for older veterans with mild to moderate gait and balance problems.

MeSH Terms

-

Keywords

Tai Chi; balance; exercise; gait; geriatrics

Acting Before; A Combined Strategy to Counteract the Onset and Progression of Dementia.

Abstract

Brain aging and aging-related neurodegenerative disorders are posing a significant challenge for health systems worldwide. To date, most of the therapeutic efforts aimed at counteracting dementia-related behavioral and cognitive impairment have been focused on addressing putative determinants of the disease, such as b-amyloid or tau. In contrast, relatively little attention has been paid to pharmacological interventions aimed at restoring or promoting the synaptic plasticity of the aging brain. The review will explore and discuss the most recent molecular, structural/functional, and behavioral evidence that supports the use of non-pharmacological approaches as well as cognitive-enhancing drugs to counteract brain aging and early-stage dementia.

MeSH Terms

-

Keywords

Aging; cognitive-enhancing drugs; dementia; exercise.; fMRI; hyper-connectivity; neuronal reserve; tau. excitotoxicity. glutamate. cognitive stimulation; β-amyloid

Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction.

Abstract

Cigarette smoke is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of the airways has been extensively studied, but its direct effects on pulmonary vasculature are less known. We aim to prove that pulmonary arterial remodeling in COPD patients is not just a consequence of alveolar hypoxia, but it is also due to direct effects of cigarette smoke on the pulmonary vascular bed. We have used different molecular and cell biology approaches, as well as traction force microscopy, wire myography and patch-clamp techniques in human cells and freshly isolated pulmonary arteries. Additionally, we relied on in vivo models and human samples to analyze the effects of cigarette smoke on pulmonary vascular tone alterations. Cigarette smoke extract (CSE) exposure directly promoted a hypertrophic, senescent phenotype that in turn contributed, through the secretion of inflammatory molecules, to increase the proliferative potential of non-exposed cells. Interestingly, these effects were significantly reversed by antioxidants. Furthermore, CSE affected cell contractility and dysregulated the expression and activity of the voltage-gated K+ channel Kv7.4. This contributed to impair vasoconstriction and vasodilation responses. Most importantly, the levels of this channel were diminished in the lungs of smoke-exposed mice, smokers and COPD patients. Cigarette smoke directly contributes to pulmonary arterial remodeling through increased cell senescence, as well as vascular tone alterations due to diminished levels and function of the Kv7.4 channel. Strategies targeting these pathways may lead to novel therapies for COPD.

MeSH Terms

-

Keywords

COPD; cell senescence; cigarette smoke; vascular remodeling; voltage-gated potassium channels

Trajectories of Body Composition during Advanced Aging in Consideration of Diet and Physical Activity: A 20-Year Longitudinal Study.

Abstract

This prospective study investigates age-dependent changes in anthropometric data and body composition over a period of two decades in consideration of physical activity and diet in community-dwelling subjects ≥60 years. Overall, 401 subjects with median follow-up time of 12 years were examined. Fat-free mass (FFM) and fat mass (FM) were analyzed using bioelectrical impedance analysis. Physical activity was assessed via a self-administered questionnaire. Dietary intake was examined by 3-day dietary records. Linear mixed-effects models were used to analyze the influence of age, sex, physical activity and energy/protein intake on anthropometric data and body composition by considering year of entry, use of diuretics and diagnosis of selected diseases. At baseline, median values for daily energy and protein intakes were 8.5 megajoule and 81 g and physical activity index was 1.7. After adjusting for covariates, advancing age was associated with parabolic changes indicating overall changes from age 60 to 90 years in women and men in body mass: -4.7 kg, -5.0 kg; body mass index: +0.04 kg/m , -0.33 kg/m ; absolute FFM: -2.8 kg, -3.5 kg; absolute FM: -1.8 kg, -1.2 kg and waist circumference: +16 cm, +12 cm, respectively. No age-dependent changes were found for upper arm circumference and relative (%) FFM. Dietary and lifestyle factors were not associated with changes in anthropometric or body composition parameters. In summary, the results indicate non-linear age-dependent changes in anthropometric data and body composition, which are largely unaffected by the degree of habitual physical activity and dietary protein intake in well-nourished community-dwelling subjects.

MeSH Terms

-

Keywords

aging; anthropometric data; body composition; longitudinal changes; physical activity; protein intake

Improving care for residents in long term care facilities experiencing an acute change in health status.

Abstract

Long term care (LTC) facilities provide health services and assist residents with daily care. At times residents may require transfer to emergency departments (ED), depending on the severity of their change in health status, their goals of care, and the ability of the facility to care for medically unstable residents. However, many transfers from LTC to ED are unnecessary, and expose residents to discontinuity in care and iatrogenic harms. This knowledge translation project aims to implement a standardized LTC-ED care and referral pathway for LTC facilities seeking transfer to ED, which optimizes the use of resources both within the LTC facility and surrounding community. We will use a quasi-experimental randomized stepped-wedge design in the implementation and evaluation of the pathway within the Calgary zone of Alberta Health Services (AHS), Canada. Specifically, the intervention will be implemented in 38 LTC facilities. The intervention will involve a standardized LTC-ED care and referral pathway, along with targeted INTERACT® tools. The implementation strategies will be adapted to the local context of each facility and to address potential implementation barriers identified through a staff completed barriers assessment tool. The evaluation will use a mixed-methods approach. The primary outcome will be any change in the rate of transfers to ED from LTC facilities adjusted by resident-days. Secondary outcomes will include a post-implementation qualitative assessment of the pathway. Comparative cost-analysis will be undertaken from the perspective of publicly funded health care. This study will integrate current resources in the LTC-ED pathway in a manner that will better coordinate and optimize the care for LTC residents experiencing an acute change in health status.

MeSH Terms

-

Keywords

Community Paramedicine; Emergency departments; Geriatrics; Long term care; Long-term care; Mixed methods; Quality of care

Mini-Review on Lipofuscin and Aging: Focusing on The Molecular Interface, The Biological Recycling Mechanism, Oxidative Stress, and The Gut-Brain Axis Functionality.

Abstract

Intra-lysosomal accumulation of the autofluorescent "residue" known as lipofuscin, which is found within postmitotic cells, remains controversial. Although it was considered a harmless hallmark of aging, its presence is detrimental as it continually accumulates. The latest evidence highlighted that lipofuscin strongly correlates with the excessive production of reactive oxygen species; however, despite this, lipofuscin cannot be removed by the biological recycling mechanisms. The antagonistic effects exerted at the DNA level culminate in a dysregulation of the cell cycle, by inducing a loss of the entire internal environment and abnormal gene(s) expression. Additionally, it appears that a crucial role in the production of reactive oxygen species can be attributed to gut microbiota, due to their ability to shape our behavior and neurodevelopment through their maintenance of the central nervous system.

MeSH Terms

-

Keywords

aging; autophagy; gut–brain axis; lipofuscin; molecular biology; oxidative stress

Effects of Aging on Expression of [i]Mic60[/i] and [i]OPA1[/i] and Mitochondrial Morphology in Myocardium of Tibetan Sheep.

Abstract

In order to investigate the effects of aging on the expression of [i]Mic60[/i] and [i]OPA1[/i] and mitochondrial morphology in plateau animals, the expression of [i]Mic60[/i] and [i]OPA1[/i] genes and proteins, and the morphology of mitochondria in the myocardium of adult and aged Tibetan sheep were investigated. The expression of [i]Mic60[/i] and [i]OPA1[/i] genes and [i]OPA1[/i] protein were higher ([i]p[/i] < 0.05) in the myocardium of adult Tibetan sheep than in those of the aged ones. The number of mitochondrial cristae in the myocardium of adult was higher than that in aged ([i]p[/i] < 0.05). The density of mitochondria in the myocardium of adult was higher than that in aged ([i]p[/i] < 0.01). Compared with the adult Tibetan sheep, the mitochondrial crista of aged were relatively sparse, the crista membrane was wide, and the mitochondria were not closely linked, showing fragmentation. These results suggest that the myocardial mitochondria of the adult have better energy supply ability, indicating that aging can lead to the weakening of oxygen supply in the myocardial mitochondria of Tibetan sheep.

MeSH Terms

-

Keywords

Mic60; OPA1; Tibetan sheep; aging; myocardial mitochondria

Examining the effects of training on young and older adult implementation of spaced retrieval strategies.

Abstract

Although the benefits of spaced retrieval are well established, research suggests that young and older adults often fail to optimally implement this strategy. The present study examined how task experience with feedback influenced participant-implemented spaced retrieval and its effect on short and long-term memory retention. Young and older adults were instructed to either equally space or expand their retrieval of face-name associations throughout an ongoing reading task. Participants were then provided feedback on the accuracy with which they implemented experimenter instructions. Results showed that feedback improved utilization of retrieval practice in both young and older adults. Moreover, both age groups successfully produced a pattern of expanded retrieval when instructed to do so, but failed to properly implement equal spacing. Consistent with extant research utilizing experimenter-determined spaced retrieval schedules, our study showed that the inclusion of a longer spacing interval immediately following acquisition resulted in reduced forgetting across the retention interval.

MeSH Terms

-

Keywords

Memory; aging; metacognition; spaced retrieval; testing effect

Neighborhood social environment and changes in leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA).

Abstract

Given limited research on the impact of neighborhood environments on accelerated biological aging, we examined whether changes in neighborhood socioeconomic and social conditions were associated with change in leukocyte telomere length using 10 years of longitudinal data from the Multi-Ethnic Study of Atherosclerosis (years 2000-2011; N = 1031; mean age = 61, SD = 9.4). Leukocyte telomere length change was corrected for regression to the mean and neighborhood was defined as census tract. Neighborhood socioeconomic indicators (factor-based score of income, education, occupation, and wealth of neighborhood) and neighborhood social environment indicators (aesthetic quality, social cohesion, safety) were obtained from the U.S Census/American Community Survey and via study questionnaire, respectively. Results of linear mixed-effects models showed that independent of individual sociodemographic characteristics, each unit of improvement in neighborhood socioeconomic status was associated with slower telomere length attrition over 10-years (β = 0.002; 95% Confidence Interval (CI): 0.0001, 0.004); whereas each unit of increase in safety (β = -0.043; 95% CI: -0.069, -0.016) and overall neighborhood social environment score (β = -0.005; 95% CI: -0.009, -0.0004) were associated with more pronounced telomere attrition, after additionally adjusting for neighborhood socioeconomic status. This study provides support for considerations of the broader social and socioeconomic contexts in relation to biological aging. Future research should explore potential psychosocial mechanisms underlying these associations using longitudinal study designs with repeated observations.

MeSH Terms

-

Keywords

Biological aging; Neighborhood social environment; Neighborhood socioeconomic disadvantage; Telomere length

Absorption properties and forcing efficiency of light-absorbing water-soluble organic aerosols: Seasonal and spatial variability.

Abstract

Light-absorbing organic aerosols, also known as brown carbon (BrC), enhance the warming effect of the Earth's atmosphere. The seasonal and spatial variability of BrC absorption properties is poorly constrained and accounted for in the climate models resulting in a substantial underestimation of their radiative forcing estimates. This study reports seasonal and spatial variability of absorption properties and simple forcing efficiency of light-absorbing water-soluble organic carbon (WSOC, SFE ) by utilizing current and previous field-based measurements reported mostly from Asia along with a few observations from Europe, the USA, and the Amazon rainforest. The absorption coefficient of WSOC at 365 nm (b ) and the concentrations of carbonaceous species at Kanpur were about an order of magnitude higher during winter than in the monsoon season owing to differences in the boundary layer height, active sources and their strengths, and amount of seasonal wet precipitation. The WSOC aerosols during winter exhibited ∼1.6 times higher light absorption capacity than in the monsoon season at Kanpur site. The assessment of spatial variability of the imaginary component of the refractive index spectrum (k ) across South Asia has revealed that it varies from ∼1 to 2 orders of magnitude and light absorption capacity of WSOC ranges from 3 to 21 W/g. The light absorption capacity of WSOC aerosols exhibited less spatial variability across East Asia (5-13 W/g) when compared to that in the South Asia. The photochemical aging of WSOC aerosols, indicated by the enhancement in WSOC/OC ratio, was linked to degradation in their light absorption capacity, whereas the absorption Ångström exponent (AAE) remained unaffected. This study recommends the adoption of refined climate models where sampling regime specific absorption properties are calculated separately, such that these inputs can better constrain the model estimates of the global effects of BrC.

MeSH Terms

-

Keywords

Absorption ångström exponent; Asia; Light absorption capacity; Photochemical aging; Refractive index

Genetic Inhibition of sFRP3 Prevents Glial Reactivity in a Mouse Model of Accelerated Aging.

Abstract

Aging is the most significant risk factor for neurodegenerative disorders that are typified by cognitive deficits. Our recent work utilizing BubR1 hypomorphic (BubR1H/H) mice, an accelerated aging model, has revealed that genetic inhibition of the endogenous Wnt pathway inhibitor secreted frizzled related protein 3 (sFRP3) plays a neuroprotective role. Neuroinflammation has been suggested as a pathological hallmark of age-related neurodegeneration mediating cognitive impairment. However, whether sFRP3 inhibition has a neuroprotective effect on neuroinflammatory gliosis in BubR1H/H mice is unknown. To investigate neuroprotection from aging-related neuroinflammation by sFRP3 in vivo, we generated double Bub R1H/H;sfrp3 knockout mice and performed immunohistological analysis with cell type-specific markers for astrocytes (glial fibrillary acidic protein), and microglia (ionized calcium-binding adapter molecule 1). Given that the hippocampus is a brain structure critical for learning and memory, and is uniquely affected in aging-related neurodegeneration, we evaluated morphological changes on astrocytes and microglia via confocal imaging. We demonstrate that BubR1H/H mice exhibit significantly increased levels of astrogliosis and an increased trend of microglial activation in the hilus and molecular layer of the young adult hippocampus, thus suggesting that BubR1 insufficiency accelerates glial reactivity. Importantly, our results further show that genetic inhibition of sFRP3 significantly recovers the astrogliosis and microglial activation observed in BubR1H/H mice, suggesting a critical neuroprotective role for sFRP3 in age-related neuroinflammation. Our findings suggest that sFRP3 inhibition may represent a novel therapeutic strategy for neurodegeneration.

MeSH Terms

-

Keywords

Aging; BubR1H/H mice; Neuroinflammation; Neuroprotection; sFRP3

Impairment of the cholinergic anti-inflammatory pathway in older subjects with severe COVID-19.

Abstract

---

MeSH Terms

-

Keywords

Alzheimer’s disease; COVID-19; Cholinergic anti-inflammatory pathway (CAP); Immunosenescence