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C-reactive protein precursor [Contains: C-reactive protein(1-205)] [PTX1]

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

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.


Keywords

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


Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.

Chronic low-grade inflammation is receiving much attention as a critical pathology that induces various aging phenotypes, a concept known as "inflammaging". Uremic patients undergoing hemodialysis therapy show vascular aging phenotypes characterized by greater arterial stiffness and calcification compared to healthy controls of the same generation. In the current study, we investigated whether levels of inflammaging markers in the circulation were associated with vascular aging phenotypes in hemodialysis patients, as estimated by the cardio-ankle vascular index (CAVI). We conducted a multicenter cross-sectional study of 412 patients receiving hemodialysis and evaluated the relationship between circulating hs-CRP or ANGPTL2 levels, as markers of inflammaging, and CAVI. Of 412 patients, 376 were analyzed statistically. While circulating hs-CRP levels had no significant association with CAVI, generalized linear models revealed that high circulating ANGPTL2 levels were significantly associated with increasing CAVI after adjustment for classical metabolic factors and hemodialysis-related parameters [β 0.63 (95%CI 0.07-1.18)]. Exploratory analysis revealed that high circulating ANGPTL2 levels were also strongly associated with increased CAVI, particularly in patients with conditions of increased vascular mechanical stress, such elevated blood pressure [β 1.00 (95%CI 0.23-1.76)], elevated pulse pressure [β 0.75 (95%CI 0.52-0.98)], or excess body fluid [β 1.25 (95%CI 0.65-1.84)]. We conclude that circulating levels of ANGPTL2 rather than hs-CRP are positively associated with CAVI in the uremic population and that ANGPTL2 could be a unique marker of progression of vascular aging in patients receiving hemodialysis.


Keywords

  • Angiopoietin-like protein (ANGPTL) 2
  • Cardio-ankle vascular index (CAVI)
  • Chronic inflammation
  • Hemodialysis
  • Senescence


Cardiovascular rehabilitation in patients aged 70-year-old or older: benefits on functional capacity, physical activity and metabolic profile in younger [i]vs[/i]. older patients.

The benefits of exercise-based cardiac rehabilitation (EBCR) programs in post-acute myocardial infarction (AMI) patients have been demonstrated. Our aim was to assess the impact of EBCR in ≥ 70-years-old [i]vs.[/i] younger post-AMI patients. We retrospectively evaluated patients who underwent a supervised EBCR protocol, twice a week during 6-12 weeks. We evaluated changes in several outcomes based on pre- and post-CRP assessments. Of a total of 1607 patients, 333 (21%) were ≥ 70-years-old. After the EBCR, an overall improvement on functional capacity, daily physical activity, lipid profile, body mass index, glycated hemoglobin (HbA1c), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and C-reactive protein was observed in both younger and older patients ([i]P[/i] < 0.05). Older patients showed a smaller benefit on the increment of daily physical activity and lipid profile improvement, but a larger reduction in NT-pro-BNP. In the multivariate analysis, only improvements on daily physical activity and HbA1c were dependent on age. As their younger counterparts, older patients, significantly improved functional capacity, metabolic parameters and level of daily physical activity after EBCR.


Keywords

  • Aging
  • Cardiovascular prevention
  • Exercise-based cardiac rehabilitation


rRT-PCR Results of a Covid-19 Diagnosed Geriatric Patient.

In this study, we aimed to present a geriatric patient with the diagnosis of COVID-19 and with contradictory results in rRT-PCR examinations in short time intervals. A 69-year-old male patient was admitted to the emergency room on the 18th day of May 2020, with the complaints of fever, sweating, myalgia, dry cough that continued for 5 days, and the lack of taste that started on the day he applied to the emergency room. Comorbidity factors include diabetes mellitus, bronchial asthma, and hypertension. The patient has a history of 36 years of smoking 1.5 packs per day. High laboratory findings during hospitalization: monocytes, creatinine, CRP (C-reactive protein). In the thorax CT, in the parenchyma areas of both lungs, there are increases in attenuation with multilobe distributions (more visible at the level of the upper lobes) in the form of ground-glass opacities. May 19, 2020, was subjected to the rRT-PCR test, repeated twice on the 19th of May which also resulted in positive. Despite rRT-PCR tests, which were negative on 27th of May and positive on 28th of May, the patient, whose symptoms disappeared, and general condition improved, was discharged on June 1, 2020, with the recommendation for home isolation. In our case, unlike the incubation period only, we encountered a negative rRT-PCR result on the 8th day after diagnosis. Therefore, the COVID-19 pandemic control and filiation evaluation with the rRT-PCR test may produce false negative results.


Keywords

  • COVID-19
  • False negative reactions
  • Geriatrics
  • Mass screening
  • Reverse transcriptase polymerase chain reaction
  • SARS-CoV-2
  • Tomography


The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality.

The association between aging and idiopathic pulmonary fibrosis is established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated. Evaluate associations between aging biomarkers, ILA, and all-cause mortality. In the Framingham Heart Study (FHS), we evaluated associations between plasma biomarkers (interleukin-6 [IL-6], C-reactive protein [[[CRP]]], tumor necrosis factor alpha receptor II [TNFR], growth differentiation factor 15 [[[GDF15]]], cystatin-C, hemoglobin A1C [HGBA1C], insulin, insulin like growth factor [IGF] 1, and IGF binding proteins 1 and 3 [[[IGFBP1]] and 3]), ILA, and mortality. Causal inference analysis was used to determine if biomarkers mediated age. GDF15 results were replicated in COPDGene. In FHS, there was higher odds of ILA per increase in natural log-transformed (ln) GDF15 (OR [95% CI] = 3.4 [1.8-6.4], p=0.0002), TNFR (3.1 [1.6-5.8], p=0.004), IL-6 (1.8 [1.4-2.4], p<0.0001), and CRP (1.7 [1.3-2.0], p<0.0001). In FHS, after adjustment for multiple comparisons, no biomarker was associated with increased mortality, but GDF15 (HR = 2.0 [1.1-3.5], P=0.02), TNFR (1.8 [1.0-3.3], p=0.05), and IGFBP1 (1.3 [1.1-1.7], P=0.01) approached significance. In COPDGene, higher ln(GDF15) was associated with ILA (OR = 8.1 [3.1-21.4], p<0.0001) and mortality (HR = 1.6 [1.1-2.2], p=0.01). Causal inference analysis showed the association of age with ILA was mediated by IL-6 (p<0.0001), TNFR (p=0.002), and likely GDF15 (p=0.008) in FHS, and by GDF15 (p=0.001) in COPDGene. Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the association between age, ILA, and mortality.


Keywords

  • aging
  • growth differentiation factor 15
  • idiopathic pulmonary fibrosis
  • interstitial lung abnormalities
  • mortality


A Novel Fortified Dairy Product and Sarcopenia Measures in Sarcopenic Older Adults: A Double-Blind Randomized Controlled Trial.

To evaluate the efficacy of daily consumption of fortified yogurt with beta-Hydroxy beta-Methyl Butyrate (HMB) and vitamins D and C on measures of sarcopenia, inflammation, and quality of life in sarcopenic older adults. In this 12-week randomized double-blind controlled trial, participants received either yogurt fortified with 3 g HMB, 1000 IU vitamin D, and 500 mg vitamin C in the intervention group (n = 33) or plain yogurt in the control group (n = 33). A total of 66 older adults with sarcopenia recruited from the community in Shiraz, Iran. Body composition, muscle strength, and functionality were measured using Dual-energy-X-ray Absorptiometry (DXA), hydraulic handgrip dynamometer, and usual gait speed, respectively. Serum concentrations of vitamin D, insulin-like growth factor-1 (IGF-1), C-reactive protein (hs-CRP), malondialdehyde, and insulin were measured at baseline and after 12 weeks. Health-related quality of life (HRQoL) was also evaluated using SF-12 questionnaire. Consumption of fortified yogurt was associated with improvement in handgrip strength [mean change (95% confidence interval) 4.36 (3.35-5.37) vs. 0.97 (-0.04 to 1.99)] and gait speed [0.10 (0.07-0.13) vs. 0.01 (0.00-0.04)] in the intervention group compared with the control group (P < .001). In addition, the results revealed a significant increase in vitamin D and IGF-1 levels in the intervention group (P < .001). The nutritional intervention significantly prevented any increase in the serum concentration of hs-CRP compared with the control group (P = .033). The results also showed a more significant decrease in the malondialdehyde level in the intervention group compared with the control (P = .008). Moreover, there were significant differences between the 2 groups regarding physical aspects of HRQoL (P = .035). A novel dairy product fortified with HMB, vitamin D, and vitamin C not only could enhance muscle strength and functionality, but also modulate anabolic and inflammatory conditions as well as quality of life. This study suggested that specific nutritional interventions alone could be beneficial, especially for those who are unable to exercise.


Keywords

  • Functional food
  • aging
  • beta-hydroxy beta-methylbutyrate
  • muscle strength
  • sarcopenia
  • vitamin D


Age-Related Colonic Mucosal Microbiome Community Shifts in Monkeys.

Aging-related changes in gut microbiome changes impacts host health. The interactive relationship between the microbiome and physiological systems in an aged body system remains to be clearly defined, particularly in the context of inflammation. Therefore, we aimed to evaluate systemic inflammation, microbial translocation (MT) and differences between fecal and mucosal microbiomes. Ascending colon mucosal biopsies, fecal and blood samples from healthy young and old female vervet monkeys were collected for 16S rRNA gene sequencing, MT and cytokine analyses, respectively. To demonstrate microbial co-occurrence patterns, we used Kendall's tau correlation measure of interactions between microbes. We found elevated levels of plasma LBP-1, MCP-1 and CRP in old monkeys, indicative of higher MT and systemic inflammation. Microbiome analysis revealed significant differences specific to age. At the phylum level, abundances of pathobionts such as Proteobacteria were increased in the mucosa of old monkeys. At the family level, Helicobacteriaceae was highly abundant in mucosal samples (old); in contrast, Ruminococcaceae were higher in fecal samples old monkeys. We found significantly lower Firmicutes:Bacteroidetes ratio and lower abundance of butyrate-producing microbes in old monkeys, consistent with less healthy profiles. Microbial community co-occurrence analysis on mucosal samples revealed 13 nodes and 41 associations in the young monkeys, but only 12 nodes and 21 associations in the old monkeys. Our findings provided novel insights into systemic inflammation and gut microbial interactions, highlights the importance of the mucosal niche, and facilitates further understanding of the decline in the stability of the microbial community with aging.


Keywords

  • Aging
  • Microbial co-occurrences
  • Mucosal microbiome
  • Systemic inflammation


The relationship between frailty and serum alpha klotho levels in geriatric patients.

Frailty is a medical syndrome resulting in loss of endurance, strength and physiological function. There is insufficient data to understand the process of frailty formation at the gene level, however one of the product of Klotho gene known as an anti-aging gene with many functions that prolong lifespan is alpha klotho protein. We aimed to investigate the relationship between frailty and the serum alpha klotho protein levels. In this cross-sectional analysis, there were 89 patients aged 65 years old and older, 45 of whom were frail and 44 of whom were not frail, were included in the study. Within the scope of the study, a sociodemographic and clinical information form, the Turkish version of the FRAIL scale and a comprehensive geriatric assessment were evaluated. In addition to routine laboratory tests, plasma alpha klotho protein levels were measured. The mean alpha klotho protein levels of the patients were 0.76 ± 1.01 ng/ml in the control group and 0.54 ± 0.61 ng/ml in the frail group, however, there was no statistically significant difference between the two groups (p = 0.286). C-reactive protein (CRP) levels were significantly higher and hemoglobin (Hb) levels were significantly lower in the frail patients compared to the control group (p < 0.05). It was observed that alpha klotho protein level was inversly correlated with increased CRP levels but association was weak (p = 0.022, R: -0.245). Hb levels (p = 0.018, R: 0.250) was weakly correlated with alpha klotho protein level. No significant relationship was found between frailty and alpha klotho protein levels in the geriatric patients. Further comprehensive studies are needed to explore this subject.


Keywords

  • Aging
  • Biomarkers
  • Frailty syndrome
  • Geriatric syndrome
  • Sarcopenia


ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA.

Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A-also called progerin-causes Hutchinson-Gilford progeria syndrome a well-known premature aging disease. Minor levels of progerin are readily expressed in the blood of healthy individuals due to alternative splicing. Previously, we found an association of increased progerin mRNA with overweight and chronic inflammation (hs-CRP). Here, we aimed to elucidate correlations of ZMPSTE24, lamin A/C and progerin with the inflammatory marker hs-CRP. In this retrospective, cross-sectional study we analyzed blood samples from 110 heart failure patients for quantitative mRNA expression of ZMPSTE24, lamin A/C, progerin and hs-CRP protein. Spearman correlations and linear regression analyses including adjustments for age, gender and ejection fraction showed a significant positive correlation of lnprogerin with lnZMPSTE24 (n = 110; r = 0.33; [i]p[/i] = 0.0004) and lnlamin A/C (n = 110; r = 0.82, [i]p[/i] < 0.0001), whereas no association was observed between lnlamin A/C and lnZMPSTE24 expression. Further analyses showed a significant positive correlation of lnhs-CRP with lnZMPSTE24 (n = 110; r = 0.21; [i]p[/i] = 0.01) and lnlamin A/C (n = 110; r = 0.24; [i]p[/i] = 0.03). We conclude that chronic inflammation is associated with increased expression of ZMPSTE24 and lamin A/C mRNA. Both markers also positively correlate with increased expression of the premature aging marker progerin which may be linked to cardiovascular aging.


Keywords

  • ZMPSTE24
  • aging
  • inflammation
  • lamin A/C
  • progerin


Synergistic antioxidant capacities of vanillin and chitosan nanoparticles against reactive oxygen species, hepatotoxicity, and genotoxicity induced by aging in male Wistar rats.

This study aimed to evaluate the synergistic effects of both vanillin (V) and chitosan nanoparticles (CNPs) in alleviating hepatotoxicity, oxidative injury, and genotoxicity induced by d-galactose (DG) and resulted from aging in male albino rats. Male Wistar rats were divided into seven groups (10 rats/group) as follows: control group, (DG) group (100 mg/kg), (V) group (100 mg/kg), CNPs either (low dose (LD) or CNPs (high dose (HD) (140 mg/kg) and (280 mg/kg), and CNPs (LD and HD) dose with V- and DG plus V-treated groups. The CNPs were characterized by transmission electron microscopy (TEM), zeta potential, and size distribution of nanoparticles. After 60 consecutive days of exposure, some biochemical parameters were measured as hepatic aminotransferases enzymes, lipid profile, tumor necrosis factor alpha, interleukin-6 (IL-6), markers of inflammation, tissue damage lactate dehydrogenase, C-reactive protein (CRP), mitochondrial potential activities, myeloperoxidase, xanthine oxidase, CRP, succinate dehydrogenase, mitochondria membrane potential, malondialdehyde levels and antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase), and adenosine triphosphate content with histological, alkaline comet assay, and TEM examination of the hepatic tissues. CNPs showed that size distribution (polydispersity index) 0.350 nm and the zeta potential measurement of CNPs were found to be -14.9 mV which revealed the high stability of CNPs. DG induced biochemical and cellular alterations in the hepatic tissues. CNPs and V synergistically afforded protection against hepatic injury and oxidative stress resulting from aging that was induced by DG. Consequently, CNPs were an effective agent in the drug delivery in the hepatic diseases medications and act as a carrier for V and thus make synergistic effect between CNPs and V that achieved the high antioxidant capacities. CNPs and V improved the hepatic enzymes, which act as anti-inflammatory and antigenotoxicity, and improved the antioxidant capacities in the hepatic tissues.


Keywords

  • Aging
  • antioxidant
  • chitosan nanoparticles
  • hepatotoxicity
  • metabolic dysfunction
  • oxidative stress
  • vanillin


Cultural and life style practices associated with low inflammatory physiology in Japanese adults.

Japan is an exceptionally healthy East Asian country with extended longevity. In addition, the typical levels of several proinflammatory proteins, including both C-reactive protein (CRP) and interleukin-6 (IL-6), are often reported to be low when compared to American and European populations. This analysis determined if blood levels of CRP and IL-6 were associated with 4 cultural practices reflective of Japanese behavior and customs -- drinking tea, eating seafood, consuming vegetables, and partaking in relaxing baths regularly - among 382 adults living in Tokyo. Regression models controlled for demographic factors, adiposity (BMI), physical exercise, smoking, alcohol use, and chronic illness (e.g., diabetes). Consuming a Japanese diet was associated with significantly lower CRP and IL-6 levels. More frequent bathing was associated with lower IL-6, but not specifically predictive of low CRP. This study has confirmed prior evidence for low inflammatory activity in Japanese adults and its association with several behavioral practices common in Japan.


Keywords

  • Aging
  • Bathing
  • C-reactive protein
  • Diet
  • Inflammation
  • Interleukin-6
  • Japan
  • Tea


Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy.

The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-α, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all [i]p[/i] < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART.


Keywords

  • HIV
  • aging
  • anti-retroviral therapy
  • inflammation
  • morbidity


Circulating biomarkers characterizing physical frailty: CRP, hemoglobin, albumin, 25OHD and free testosterone as best biomarkers. Results of a meta-analysis.

During aging, individuals can be classified as being in one of 3 different states: robust, frail or dependent. Frailty is described as reversible, so early detection offers the potential of returning the subject to a robust status. There are multiple clinical frailty scales but no gold standard and frailty is not systematically assessed in clinicians' daily practice. Reliable biomarkers of frailty are lacking, however, while their identification and systematic use would make this simple scale a useful clinical tool. To conduct a review of the literature concerning the biomarkers associated with frailty and to compare in a meta-analysis the plasmatic values of each biomarker in the frail with the robust group. 503 articles were identified on PubMed, 467 on Scopus and 369 on Web Of Science. 67 articles were included, collecting a total of 32,934 robust subjects and 6864 frail subjects. C-reactive protein (CRP) (Standardized Mean Difference (SMD): 0.49 CI 95% [0.37-0.61]) was significantly higher in the frail group whereas hemoglobin (SMD: -0.67[-0.90; -0.44]), albumin (SMD: -0.62[-0.84; -0.41]), 25-hydroxyvitamin D (25OHD) (SMD: -0.43 [-0.64; -0.21]) and, in men, free testosterone (SMD: -0.77 [-1.05; -0.49]) were significantly lower in the frail group. We found 5 biomarkers that were associated with frailty (CRP, hemoglobin, albumin, 25OHD and free testosterone in men) belonging to multiple physiological systems. Further cohort studies are needed to verify their ability to screen for frailty.


Keywords

  • Aging
  • Biomarkers
  • Frailty
  • Meta-analysis


The beneficial effect of physical exercise on inflammatory makers in older individuals.

Old age is associated with a loss of motor functions and a general progressive decline in cognitive functions. Physical exercise is one of the ways in which inflammatory levels in general can be reduced, and therefore physical exercise can be considered a biological aging decelerator. In this article we examine the relationships between physical exercise and inflammatory markers reported for the different physical exercise protocols that have been used in studies with older individuals, as well as the effects of these regimens. The different types of exercises programmed, and methods used to implement them were very heterogeneous in the articles we analysed. Both, the aerobic exercise and resistance training protocols produced a decrease in plasma levels of IL-6, CRP and TNF-α, and an increase of IL10 plasma levels as a chronic effect. However, the acute-response of physical exercise appeared to be an initial increase in IL-6 expression and plasma IL-6 levels. Continuing with these exercise programs usually subsequently achieved a chronic response in which there was a decrease in both the basal levels of IL-6, CRP and TNF-α, and the IL-6 produced as acute responses. Regardless of the type of exercise performed, it seems that the exercise parameters, intensity, duration, subject variables, fitness, and level of inflammation are key factors in achieving the expected balance between pro-inflammatory and antiinflammatory cytokines.


Keywords

  • IL-6 expression
  • Inflammatory markers
  • aerobic exercise
  • aging
  • plasma IL-6 levels
  • resistance training


Moderate- to high intensity aerobic and resistance exercise reduces peripheral blood regulatory cell populations in older adults with rheumatoid arthritis.

Exercise can improve immune health and is beneficial for physical function in patients with rheumatoid arthritis (RA), but the immunological mechanisms are largely unknown. We evaluated the effect of moderate- to high intensity exercise with person-centred guidance on cells of the immune system, with focus on regulatory cell populations, in older adults with RA. Older adults (≥65 years) with RA were randomized to either 20-weeks of moderate - to high intensity aerobic and resistance exercise ([i]n[/i] = 24) or to an active control group performing home-based exercise of light intensity ([i]n[/i] = 25). Aerobic capacity, muscle strength, DAS28 and CRP were evaluated. Blood samples were collected at baseline and after 20 weeks. The frequency of immune cells defined as adaptive regulatory populations, CD4   Foxp3   CD25   CD127- T regulatory cells (Tregs) and CD19   CD24hiCD38hi B regulatory cells (Bregs) as well as HLA-DR-/lowCD33   CD11b   myeloid derived suppressor cells (MDSCs), were assessed using flow cytometry. After 20 weeks of moderate- to high intensity exercise, aerobic capacity and muscle strength were significantly improved but there were no significant changes in Disease Activity Score 28 (DAS28) or CRP. The frequency of Tregs and Bregs decreased significantly in the intervention group, but not in the active control group. The exercise intervention had no effect on MDSCs. The reduction in regulatory T cells in the intervention group was most pronounced in the female patients. Moderate- to high intensity exercise in older adults with RA led to a decreased proportion of Tregs and Bregs, but that was not associated with increased disease activity or increased inflammation. Improved Ability to Cope With Everyday Life Through a Person-centered Training Program in Elderly Patients With Rheumatoid Arthritis - PEP-walk Study, NCT02397798. Registered at ClinicalTrials.gov March 19, 2015.


Keywords

  • Aging
  • Breg cells
  • Exercise
  • IL-10
  • Rheumatoid arthritis
  • T cells
  • Treg cells


PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation.

Longevity gene klotho (KL) is associated with age-related phenotypes including lifespan, cardiometabolic disorders, cognition, and brain morphology, in part, by conferring protection against inflammation. We hypothesized that the KL/inflammation association might be altered in the presence of psychiatric stress and operate via epigenetic pathways. We examined KL polymorphisms, and their interaction with posttraumatic stress disorder (PTSD) symptoms, in association with KL DNA methylation in blood. We further examined KL DNA methylation as a predictor of longitudinal changes in a peripheral biomarker of inflammation (C-reactive protein; CRP). The sample comprised 309 white non-Hispanic military veterans (93.5 % male; mean age: 32 years, range: 19-65; 30 % PTSD per structured diagnostic interview); 111 were reassessed approximately two years later. Analyses revealed a methylation quantitative trait locus at rs9527025 (C370S, previously implicated in numerous studies of aging) in association with a Cytosine-phosphate-Guanine site (cg00129557; B = -.65, p =  1.29 X 10 ), located within a DNase hypersensitivity site in the body of KL. There was also a rs9527025 x PTSD severity interaction (B = .004, p = .035) on methylation at this locus such that the minor allele was associated with reduced cg00129557 methylation in individuals with few or no PTSD symptoms while this effect was attenuated in those with elevated levels of PTSD. Path models revealed that methylation at cg00129557 was inversely associated with CRP over time (B = -.14, p = .005), controlling for baseline CRP. There was also an indirect effect of rs9527025 X PTSD on subsequent CRP via cg00129557 methylation (indirect B = -.002, p = .033). Results contribute to our understanding of the epigenetic correlates of inflammation in PTSD and suggest that KL methylation may be a mechanism by which KL genotype confers risk vs. resilience to accelerated aging in those experiencing traumatic stress.


Keywords

  • Accelerated aging
  • Inflammation
  • Klotho
  • Methylation
  • PTSD


Ultrasound-guided continuous thoracic paravertebral block alleviates postoperative delirium in elderly patients undergoing esophagectomy: A randomized controlled trial.

Delirium is a common postoperative complication in older patients undergoing thoracic surgery and presages poor outcomes. Postoperative pain is an important factor in the progression of delirium. The purpose of this study was to test whether continuous thoracic paravertebral block (PVB), a more effective approach for analgesia, could decrease the incidence of delirium in elderly patients undergoing esophagectomy. A total of 180 geriatric patients undergoing esophagectomy were randomly divided into 2 groups and treated with PVB or patient-controlled analgesia (PCA). Perioperative plasma CRP, IL-1β, IL-6, and TNF-α levels were detected in all patients. Pain intensity was measured by a numerical rating scale. Delirium was assessed using the confusion assessment method. The incidence of postoperative delirium was significantly lower in the PVB group than in the PCA group. Patients in the PVB group had lower plasma CRP, IL-1β, IL-6, and TNF-α levels and less pain when coughing after surgery. Ultrasound-guided continuous thoracic paravertebral block improved analgesia, reduced the inflammatory reaction and decreased the occurrence of delirium after surgery.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Analgesia, Patient-Controlled
  • Delirium
  • Esophagectomy
  • Female
  • Geriatrics
  • Humans
  • Male
  • Middle Aged
  • Nerve Block
  • Postoperative Complications
  • Prospective Studies
  • Ultrasonography


Bereavement is associated with reduced systemic inflammation: C-reactive protein before and after widowhood.

Bereavement is associated with poorer health and early mortality. Increased systemic inflammation is one pathophysiological pathway thought to explain this health risk. However, few studies have examined systemic inflammation before and after widowhood. The current study examined the associations between inflammation and widowhood status before and after bereavement in a sample of married adults who became widowed between assessments in the English Longitudinal Study of Ageing. We examined levels and change over time in systemic inflammation, as assessed by C-reactive protein (CRP), among participants who became bereaved (n = 199). We then compared these results to a sample of participants whose spouse remained living, selected using a propensity score matching algorithm (n = 199). Contrary to expectations, widowed participants' CRP decreased following bereavement, d = -0.29, p < 0.001. Change in CRP was not associated with pre-loss depression levels, caregiving status, marital quality, number of chronic diseases, prescribed medications, body mass index, age, or sex. Compared to continuously married participants, widowed participants' evidenced a significantly greater decrease in CRP after their spouse's death, β = -0.14, p < 0.001. Widowed adults' systemic inflammation decreased significantly following bereavement, both as a group and compared to people who remained married. We discuss possible explanations for this counterintuitive finding, including the measure of inflammation used in the study and the timing of the study measurements.


Keywords

  • Aging
  • Bereavement
  • C-reactive protein
  • Health
  • Inflammation
  • Widowhood


The Impact of Age on the Prevalence of Sarcopenic Obesity in Bariatric Surgery Candidates.

Sarcopenia pre-dating bariatric surgery (BS) has been suggested as concern for the use of BS in older-adults with morbid obesity. To evaluate the impact of age on the prevalence of sarcopenic obesity (SO) in BS-candidates. Cross-sectional study including 1370 consecutive BS-candidates aged ≥18, and grouped according to age: 18-39 (reference group), 40-49, 50-59 and ≥ 60 years. From body composition analysis data obtained using bioelectrical impedance, skeletal muscle mass (SMM), SMM index (SMMI=SMM/height ), and percentage of SMM (%SMM = SMM/BW*100) were calculated. Class I or class II SO was adjudicated, respectively, when a value between > - 1 and - 2, or > -2 standard deviations from the regression line from the gender-specific distribution of the relationship between BMI and SMMI or the %SMM in the reference group was encountered. According to the SMMI distribution, prevalence of class I and class II SO in the whole cohort was respectively 16.4% and 4.6%. SO was more prevalent in females (p < 0.005). Proportion of subjects with SO positively correlated with older age category in females (Tau-c = 0.149, p < 0.001) but not in males. In females aged ≥60, class I SO was present in 29.1%, and class II in 12.8%. Similar results were obtained when %SMM was used (Cohen's k-coefficient = 0.886, p < 0.001). Age and female gender were identified as independent preditors of SO, whereas CRP or the presence of obesity-associated comorbidities were not. Age is a risk factor for SO in BS-candidates. SO is fairly common in female subjects aged >60 years that are candidates to BS.


Keywords

  • Aging
  • Bariatric surgery
  • Elderly
  • Obesity
  • Sarcopenia


Intake of dietary advanced glycation end products influences inflammatory markers, immune phenotypes, and antiradical capacity of healthy elderly in a little-studied population.

Dietary advanced glycation end products (dAGE) have profound negative effects on overall health, and their intake must be assessed. In this cross-sectional study, we investigated dAGE intake of 337 adult participants (180/157:M/F; age range 50-73 years). Data were collected on anthropometrics, body composition, dietary intake, selected blood biochemistry, immunological parameters, and antiradical capacity (50% hemolysis time; HT ). From the dietary data, dAGEs and phytochemical index (PI) were calculated. Mean BMI, % body fat (�), and fasting plasma glucose were all within the accepted normal range. Subjects with high dAGE intake had higher �, higher energy intake, and lower PI. They tended to have lower CD4/CD8 ratios and higher proportions of B cells and NK cells, but had significantly higher hs-CRP levels and lower HT values. Results on HT suggested that being >60 years of age enhanced dAGE-associated impairment of defense capacity in both those with low and high HT compared with those <60 years of age. Thus, overall dAGE consumption was high, but elderly participants had lower dAGE intake than younger adults. Indicators of nutritional status and immunological parameters of the subjects were found to be associated with dAGE intake, suggesting a potential impact on health.


Keywords

  • CRP
  • advanced glycationed end products
  • aging
  • dAGE
  • immunity
  • inflammation


Intentional Switching Between Bimanual Coordination Patterns in Older Adults: Is It Mediated by Inhibition Processes?

The study investigated the consequences of age-related decline in inhibition processes on intentional switching between bimanual coordination patterns. Fifteen young (24±2.8 years) and 20 older adults (69±5.3 years) performed Stroop tasks and bimanual coordination tasks. Stroop tasks included neutral, congruent, and incongruent conditions. Response time and error rate were measured. Bimanual coordination tasks consisted of performing in-phase (IP) and anti-phase (AP) patterns. Participants were requested to switch as quickly as possible from one pattern to the other, resulting in two different switching directions (AP to IP; IP to AP). Mean and standard deviation (SD) of the continuous relative phase (CRP) were calculated pre- and post-switching for each participant. Total switching time (TST) was measured. The switching phase was also decomposed into reaction time (RT) and reversal time (REvT). Pearson correlation analyses were performed to test for correlations between: (i) SD of CRP and response time in Stroop tasks, and (ii) switching times (TST, RT, RevT) and response time in Stroop task, respectively. In addition, parallel mediation analyses were conducted. Results showed that: (i) the AP pattern was less stable than the IP pattern in both young and older adults, (ii) coordination patterns were less stable in older adults, (iii) response times in Stroop task were longer in the incongruent condition, and (iv) RespTs were longer in older than in young participants, whatever the condition. In the bimanual coordination task, RT, RevT, and TST increased with age. The stability of the IP pattern was correlated with the response times observed in neutral and congruent conditions, while the stability of the AP pattern was correlated with response time observed in the incongruent condition. Correlation and mediation analyses showed that, in the AP to IP switching direction, RT and RevT were both significantly correlated with response times observed in the incongruent condition of Stroop task. These findings suggest that inhibition processes are involved in switching between bimanual coordination patterns, at least to trigger the early phase of switching. They also support the hypothesis that inhibition processes are more involved in maintaining the AP pattern and switching to the IP pattern. Finally, age-related changes in switching times seem to be prominently mediated by alterations of inhibition processes.


Keywords

  • Stroop task
  • aging
  • bimanual coordination
  • inhibition
  • mediation analysis
  • switching


Shorter Telomere Length in Peripheral Blood Leukocytes Is Associated with Post-Traumatic Chronic Osteomyelitis.

This study investigated the association between post-traumatic chronic osteomyelitis (COM) and peripheral leukocyte telomere length (PLTL) and explored factors associated with PLTL in COM. A total of 56 patients with post-traumatic COM of the extremity and 62 healthy control subjects were recruited. The PLTL was measured by real-time PCR. Binary logistic regression analysis was used to identify factors in correlation with telomere length. Sex, age, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and infection duration were included as independent variables in the logistic regression model. Post-traumatic COM patients had significantly shorter PLTLs (5.39 ± 0.40) than healthy control subjects (5.69 ± 0.46; p < 0.001). Binary logistic regression analysis showed that PLTL had a statistically significant association with age ([i]B[/i] = -0.072; p = 0.013) and CRP ([i]B[/i] = -0.061; p = 0.033). The logistic regression model was statistically significant and explained 31.4% (Nagelkerke R ) of the change in telomere length and correctly classified 69.6% of the cases. Patients with post-traumatic COM have shorter PLTLs than healthy subjects. The PLTL erosion of post-traumatic COM was partially explained by age and CRP.


Keywords

  • aging
  • post-traumatic chronic osteomyelitis
  • telomere


Risk Factors of Progression to Frailty: Findings from the Singapore Longitudinal Ageing Study.

To investigate risk factors of incident physical frailty. A population-based observational longitudinal study. Community-dwelling elderly with age 55 years and above recruited from 2009 through 2011 in the second wave Singapore Longitudinal Ageing Study-2 (SLAS-2) were followed up 3-5 years later. A total of 1297 participants, mean age of 65.6 ±0.19, who were free of physical frailty. Incident frailty defined by three or more criteria of the physical phenotype used in the Cardiovascular Health Study was determined at follow-up. Potential risk factors assessed at baseline included demographic, socioeconomic, medical, psychological factors, and biochemical markers. A total of 204 (15.7%) participants, including 81 (10.87%) of the robust and 123 (22.28%) of the prefrail transited to frailty at follow-up. Age, no education, MMSE score, diabetes, prediabetes and diabetes, arthritis, ≥5 medications, fair and poor self-rated health, moderate to high nutritional risk (NSI ≥3), Hb (g/dL), CRP (mg/L), low B12, low folate, albumin (g/L), low total cholesterol, adjusted for sex, age and education, were significantly associated (p<0.05) with incident frailty. In stepwise selection models, age (year) (OR=1.07, 95%CI=1.03-1.10, p<0.001), albumin (g/L) (OR=0.85, 95%CI=0.77-0.94, p=0.002), MMSE score (OR=0.88, 95%CI=0.78-0.98, p=0.02), low folate (OR=3.72, 95%CI=1.17-11.86, p=0.03, and previous hospitalization (OR=2.26, 95%CI=1.01-5.04,p=0.05) were significantly associated with incident frailty. The study revealed multiple modifiable risk factors, especially related to poor nutrition, for which preventive measures and early management could potentially halt or delay the development of frailty.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Disease Progression
  • Female
  • Frail Elderly
  • Frailty
  • Geriatric Assessment
  • Humans
  • Independent Living
  • Longitudinal Studies
  • Male
  • Nutrition Assessment
  • Nutritional Status
  • Physical Examination
  • Risk Factors
  • Singapore
  • Socioeconomic Factors

Keywords

  • Frailty
  • longitudinal
  • risk factors
  • transition


Physical Function and Strength in Relation to Inflammation in Older Adults with Obesity and Increased Cardiometabolic Risk.

Inflammation is implicated in functional decline and the development of disability in aging. This study aimed to investigate the association of inflammation with physical function and muscle strength in older adults with obesity and increased cardiometabolic risk. In baseline assessments from the CROSSROADS randomized controlled trial, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and C-reactive protein (hs-CRP) were assayed in 163 older adults (37% males, 24% African American, BMI 34±3, age 70±5yrs) with hypertension, dyslipidemia and/or diabetes. Physical function was assessed by six-minute walk test (6MWT), chair sit-and-reach (CSR), hand-grip and knee-extension strength; specific-strength as muscle strength/mass ratio. Analyses included ANCOVA and multiple linear regression adjusted for thigh skeletal muscle (MRI), arm lean mass (DXA) and moderate-to-vigorous intensity physical activity (MVPA; accelerometry). Higher hs-CRP (p<0.01) and IL-6 (p=0.07) were associated with lower 6MWT and CSR, respectively. A composite inflammation score combining all 3 inflammatory markers showed the strongest inverse association with 6MWT (p<0.01). MVPA moderated associations such that amongst participants who engaged in low MVPA, 6MWT distances and CSR scores were significantly lower in those with high IL-6 and TNFα (p<0.05), respectively. In participants with high MVPA, higher hs-CRP (p<0.05) and TNFα (p=0.07) were associated with poorer upper-extremity specific-strength. Chronic inflammation was associated with poorer physical function and specific strength in older adults with obesity and increased cardiometabolic risk. This association was strongest in participants with multiple elevated inflammatory markers. Physical activity levels below current recommendations mitigated the deleterious effects of inflammation on lower body mobility, underscoring the benefits of exercise for preserving physical function with age.

MeSH Terms

  • Aged
  • Aging
  • Cardiovascular Diseases
  • Female
  • Humans
  • Inflammation
  • Male
  • Muscle Strength
  • Obesity
  • Physical Exertion

Keywords

  • Inflammation
  • cardiovascular disease risk factors
  • obesity
  • physical activity
  • physical function


Key diagnostic characteristics of fever of unknown origin in Japanese patients: a prospective multicentre study.

To identify the key diagnostic features and causes of fever of unknown origin (FUO) in Japanese patients. Multicentre prospective study. Sixteen hospitals affiliated with the Japanese Society of Hospital General Medicine, covering the East and West regions of Japan. Patient aged ≥20 years diagnosed with classic FUO (axillary temperature≥38.0°C at least twice within a 3-week period, cause unknown after three outpatient visits or 3 days of hospitalisation). A total of 141 cases met the criteria and were recruited from January 2016 to December 2017. Japanese standard diagnostic examinations. Data collected include usual biochemical blood tests, inflammatory markers (erythrocyte sedimentation rate (ESR), C reactive (CRP) protein level, procalcitonin level), imaging results, autopsy findings (if performed) and final diagnosis. The most frequent age group was 65-79 years old (mean: 58.6±9.1 years). The most frequent cause of FUO was non-infectious inflammatory disease. After a 6-month follow-up period, 21.3% of cases remained undiagnosed. The types of diseases causing FUO were significantly correlated with age and prognosis. Between patients with and without a final diagnosis, there was no difference in CRP level between patients with and without a final diagnosis (p=0.121). A significant difference in diagnosis of a causative disease was found between patients who did or did not receive an ESR test (p=0.041). Of the 35 patients with an abnormal ESR value, 28 (80%) had causative disease identified. Age may be a key factor in the differential diagnosis of FUO; the ESR test may be of value in the FUO evaluation process. These results may provide clinicians with insight into the management of FUO to allow adequate treatment according to the cause of the disease.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Fever of Unknown Origin
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Prospective Studies
  • Young Adult

Keywords

  • Japan
  • aging population
  • elderly
  • erythrocyte sedimentation rate
  • fever of unknown origin
  • prospective studies


Artificial Neural Network Correlation and Biostatistics Evaluation of Physiological and Molecular Parameters in Healthy Young Individuals Performing Regular Exercise.

Studies support that regular physical activity (PA) decelerates senescence-related decline of physiological and molecular parameters in the elderly. We have addressed the other end of this spectrum: healthy and young, inactive individuals participated in a 6-month long personal trainer-guided lifestyle program. We have measured physiological and molecular parameters (differentiating high- and low responders) and their correlation with PA (sedentary status). Cluster analysis helped to distinguish individuals with high- or low PA and differentiate high- and low-responders of each parameter. The assessed cardiovascular parameters (heart rate, blood pressure, 6-min walking distance, relative VO max), body composition parameters (body fat and muscle mass percentage) metabolic parameters (glucose, insulin, HDL, LDL), immune parameters (cortisol, CRP, lymphocyte counts, hTREC) all showed improvement. Artificial neural network analysis (ANN) showed correlation efficiencies of physiological and molecular parameters using a concept-free approach. ANN analysis appointed PA as the mastermind of molecular level changes. Besides sedentary status, insulin and hTREC showed significant segregation. Biostatistics evaluation also supported the schism of participants for their sedentary status, insulin concentration and hTREC copy number. In the future ANN and biostatistics, may predict individual responses to regular exercise. Our program reveals that high responder individuals of certain parameters may be low responders of others. Our data show that moderate regular PA is essential to counteract senescence in young and healthy individuals, despite individual differences in responsiveness. Such PA may not seem important in the everyday life of young and healthy adults, but shall become the base for healthy aging.


Keywords

  • aging
  • physical activity
  • prediction
  • prevention
  • responsiveness


Decrease in Serum Vitamin D Level of Older Patients with Fatigue.

Fatigue is characterized by reduced energy level, decreased muscle strength, and a variable degree of cognitive impairment. Recent evidences seem to link vitamin D deficiency to fatigue. The aim of this study was to assess and compare vitamin D status in a cohort of older subjects with and without fatigue. We recruited a total of 480 subjects, 240 patients with fatigue and 240 controls without fatigue, from the Cannizzaro Hospital of Catania (Italy). Fatigue severity was measured by the fatigue severity scale, whereas mental and physical fatigue were measured through the Wessely and Powell fatigue scale, respectively. We also measured several blood parameters and 25-OH vitamin D. Subjects with fatigue showed lower levels of vitamin D as compared with those without fatigue. Blood levels of parameters related to fatigue were normal in both groups of subjects, however, platelet, hemoglobin, hematocrit ([i]p[/i] < 0.05), mean corpuscular volume, C-reactive protein (CRP), iron, vitamin B12, and folic acid ([i]p[/i] < 0.001) were significantly higher in the fatigue group with respect to the control group. Moreover, compared to controls, patients showed higher scores in the physical ([i]p[/i] < 0.001), mental ([i]p[/i] < 0.001), and severity ([i]p[/i] < 0.001) fatigue scales. Finally, vitamin D inversely correlated with fatigue severity ([i]r[/i] = -0.428, [i]p[/i] < 0.01), whereas creatine kinase and CRP levels did not correlate with vitamin D. In conclusion, our data showed a direct link between vitamin D and fatigue in older subjects, suggesting translational implications in the diagnosis and management of these patients.

MeSH Terms

  • Aged
  • Cohort Studies
  • Fatigue
  • Female
  • Humans
  • Male
  • Middle Aged
  • Vitamin D
  • Vitamin D Deficiency

Keywords

  • aging
  • mental fatigue
  • older
  • physical fatigue
  • sex differences
  • vitamin D


The Association between Frailty Indicators and Blood-Based Biomarkers in Early-Old Community Dwellers of Thailand.

Thailand has officially reached the status of an "aged society" and become the developing country with the 2nd largest proportion of senior citizens in Southeast Asia. A cross-sectional study of 526 early-old community dwellers was conducted for the Fried frailty phenotype assessment, This included five indicators: Weakness, slowness, physical activity, exhaustion, and weight loss. C-reactive protein (CRP), interleukin-6 (IL-6), insulin-like growth factor-1, and CD4 :CD8 Ratio which serve as blood-based biomarkers of frailty. The prevalence of frailty and pre-frail in this population was found to be 15% and 69.6% respectively and was higher among women than men. Frail ([i]n[/i] = 58) and non-frail ([i]n[/i] = 60) participants were evaluated for the associations between the frail indicators and the blood-based biomarkers. Serum levels of IL-6 and CRP from frail group were significantly elevated when compared with the non-frail counterparts ([i]p[/i] = 0.044 and 0.033, respectively), and were significantly associated with the frailty status with an Odd Ratio [OR] of 1.554-fold (95% confidence interval [CI], 1.229-1.966) and an OR of 1.011-fold (95 CI, 1.006-1.016). Decreased hand-grip strength was the only frailty indicator that was significantly associated with both inflammatory biomarkers, (OR of 1.470-fold and OR of 1.008-fold). Our study is the first to assess the frailty status among the early-old population in Thailand. These findings will encourage general practitioners to combine frailty indicators and serum biomarkers as early detection tools for at-risk older adults to achieve the goal of healthy aging.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • C-Reactive Protein
  • CD4-CD8 Ratio
  • Cross-Sectional Studies
  • Female
  • Frail Elderly
  • Frailty
  • Humans
  • Independent Living
  • Interleukin-6
  • Male
  • Middle Aged
  • Thailand

Keywords

  • C-reactive protein
  • Thailand
  • aging
  • cross-sectional study
  • frailty
  • frailty biomarkers
  • fried’s phenotypes
  • interleukin-6


Associations of C-reactive protein and homocysteine concentrations with the impairment of intrinsic capacity domains over a 5-year follow-up among community-dwelling older adults at risk of cognitive decline (MAPT Study).

The World Health Organization (WHO) recently proposed an innovative model of care focusing on functional rather than disease-based perspectives, based on a construct of intrinsic capacity (IC). This study aimed to analyze if low-grade inflammation (LGI) (chronically raised C-reactive protein - CRP) and hyperhomocysteinemia (HHcy) were associated with variation in IC domains (mobility, cognition, psychological and vitality) and in a combined IC Z-score over a 5-year follow-up among non-demented, community-dwelling older adults at risk of cognitive decline. This observational study included 1516 subjects ≥70 years (64.5% female, mean age 75.4 years, SD = 4.5), volunteers from the interventional study Multidomain Alzheimer Preventive Trial (MAPT). Plasma CRP (at baseline, 6 and 12 months) and homocysteine (at baseline) concentrations were measured. LGI was defined as having ≥2 consecutively CRP readings >3 to 10 mg/L between baseline and 12 months, and HHcy was defined as homocysteine >15 μM/L. IC domains were operationalized as follows: Psychological. Depressive symptoms evaluated by the Geriatric Depression Scale (GDS); Mobility. Assessed by the Short Physical Performance Battery (SPPB); Cognitive function. Examined by a Z-score combining four tests; Vitality. Based on hand grip strength. Outcomes were combined into a composite IC Z-score. IC Z-score decreased among groups with no inflammation and LGI after 5 years, but this decrease was more pronounced among the LGI group (unadjusted mean group difference: 0.09, 95%CI: 0.01 to 0.16; p = 0.032). Participants with HHcy also presented IC Z-score decreases over time. Combined conditions provided more pronounced declines, even after adjusting for potential confounders. LGI and HHcy were both related with impairment on the combined IC levels among older adults after a 5-year follow-up. Identifying biomarkers that strongly associate with IC may help to settle strategies aiming to prevent the incidence and slow down the evolution of age-related functional decline and care dependency.

MeSH Terms

  • Activities of Daily Living
  • Aged
  • Biomarkers
  • Body Mass Index
  • C-Reactive Protein
  • Cognitive Dysfunction
  • Depression
  • Female
  • Follow-Up Studies
  • Geriatric Assessment
  • Hand Strength
  • Homocysteine
  • Humans
  • Independent Living
  • Inflammation
  • Male
  • Mobility Limitation
  • Neuropsychological Tests
  • Prospective Studies
  • Risk Factors
  • Time Factors

Keywords

  • Aging
  • C-reactive protein
  • Homocysteine
  • Inflammation
  • Intrinsic capacity
  • Older adults


Social engagement and loneliness are differentially associated with neuro-immune markers in older age: Time-varying associations from the English Longitudinal Study of Ageing.

This study aimed to explore time-varying associations between social engagement, living status and loneliness and neuro-immune markers in older adults, and ascertain whether results are explained by socioeconomic position, health behaviours or depression. We analysed blood samples from 8780 adults aged 50 and above from the English Longitudinal Study of Ageing across three waves of data collection: 2004/5, 2008/9 and 2012/2013. We used fixed effects modelling to estimate the relationship between loneliness, social isolation, living alone and levels of fibrinogen, insulin like growth factor-1 (IGF-1), white blood cell (WBC) count and C-reactive protein (CRP), whilst accounting for all time-invariant and identified time-varying confounders. Higher levels of social engagement and living with somebody were associated with lower levels of CRP, fibrinogen and WBC, while lower levels of loneliness were associated with higher levels of IGF-1. These associations were found to be independent of time-invariant factors such as gender, medical history, previous patterns of social behaviours, unobserved aspects of social class, and genetics, and time-varying factors such as income, physical health, health behaviours, and depression. Aspects of social engagement were associated with lower levels of inflammation whilst loneliness was inversely related to the regulation of inflammation. This suggests there could be different biological pathways involved in objective and subjective aspects of social connections.

MeSH Terms

  • Aged
  • Aging
  • Biomarkers
  • Depression
  • Female
  • Health Behavior
  • Humans
  • Loneliness
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuroimmunomodulation
  • Risk Factors
  • Social Behavior
  • Social Isolation
  • Socioeconomic Factors
  • Time Factors

Keywords

  • CRP
  • Fibrinogen
  • IGF-1
  • Inflammation
  • Loneliness
  • Social isolation
  • Social support


Longitudinal analysis of loneliness and inflammation at older ages: English longitudinal study of ageing.

Loneliness has been associated with adverse health outcomes, including age-related diseases with an inflammatory etiology such as cardiovascular disease. We aimed to identify potential biological pathways linking loneliness with morbidity and mortality by examining associations of loneliness with biomarkers. Participants in the English Longitudinal Study of Ageing (n = 3239) aged 50 years or older with an average age of 64 years, provided data in waves 4 (2008/2009) and 6 (2012/2013). Linear regression conditional change models had three outcomes: C reactive protein (CRP) measured in mg/L (log transformed), fibrinogen in g/L and ferritin in g/dL. In men, the onset of loneliness indicated by answering 'no' at wave 4 and 'yes' at wave 6 to question "Much of the time during the past week, you felt lonely?" was associated with a statistically significant increase in levels of CRP (β = 0.36, 95% confidence interval (0.09 to 0.62)), plasma fibrinogen (0.18 (0.04 to 0.31)) and ferritin (41.04 (6.58 to 75.50)), after full adjustment. A statistically significant increase in CRP in men was also observed for onset of loneliness assessed with the question "How often do you feel lonely?" (0.20 (0.03 to 0.38)). These associations were not mediated by depressive symptoms. Persistent loneliness (loneliness experienced at both baseline and follow-up) assessed using the University of California Los Angeles (UCLA) loneliness scale was associated with an increase in CRP (0.11 (0.004 to 0.22)) among men. Associations of the two latter loneliness measures with fibrinogen and ferritin were mainly null. Among women, the only statistically significant association was for persistent loneliness (loneliness at both waves) identified by question "Much of the time during the past week, you felt lonely?" with a reduction in levels of ferritin (-20.62 (-39.78 to -1.46)). Men may be more susceptible to loneliness-associated disease risks signaled by biological changes, including systemic inflammation. Combined social and targeted medical interventions may help to reduce health risks associated with loneliness.

MeSH Terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • C-Reactive Protein
  • England
  • Female
  • Ferritins
  • Fibrinogen
  • Humans
  • Inflammation
  • Loneliness
  • Longitudinal Studies
  • Male
  • Middle Aged

Keywords

  • C-reactive protein
  • Ferritin
  • Fibrinogen
  • Inflammation
  • Loneliness


The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) μg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 μg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Echocardiography
  • Female
  • Humans
  • Hydrocortisone
  • Inflammation
  • Male
  • Metabolic Syndrome

Keywords

  • Aging
  • Cortisol
  • Inflammation
  • Metabolic syndrome


Recurrent circadian fasting (RCF) improves blood pressure, biomarkers of cardiometabolic risk and regulates inflammation in men.

The effects of fasting on health in non-human models have been widely publicised for a long time and emerging evidence support the idea that these effects can be applicable to human practice. In an open label longitudinal follow-up, a cohort of 78 adult men (aged 20 to 85 years) who fasted for 29 consecutive days from sunrise to sunset (16 h fasting-referred to as recurrent circadian fasting) in Pakistan, were studied. The primary outcomes of the fasting study was weight loss/recovery and the associated changes in blood pressure and circulating levels of surrogate markers linked to organ and system functions-including cardiovascular, metabolic and inflammation. Post-fasting outcomes include the regulation of physiological biomarkers. Recurrent circadian fasting with weight loss reduced blood pressure (140.6 vs. 124.2 mmHg) and markers of cardiovascular risk (~ 4-fold for resistin; triglycerides: p < 0.0001). Reduced glycemia (p < 0.0001) and the associated changes in the regulation of ketosis (β-hydroxybutyrate) were accompanied by a metabolic shift (PPARβ, osteoprotegerin), suggesting the involvement of the different physiological systems tested. Elevated orexin-A levels (p = 0.0183) in participants indicate sleep disturbance and circadian adaptation. All participants had CRP level < 2 mg/l during the fasting period and a similar trend was observed for TNFα. While most SASP molecules were decreased after the fasting period, heightened levels of IL-8 and IL-6 suggest that some inflammatory markers may be elevated by recurrent circadian fasting. Importantly, older adults reveal similar or more substantial benefits from fasting. Recurrent circadian fasting is beneficial at the cardiometabolic and inflammatory levels, especially for at-risk individuals-this is contingent on compliance towards the recommended dietary behaviour, which controls carbohydrate and caloric intake. These benefits from fasting may be particularly beneficial to older adults as they often exhibit abnormal cardiovascular, metabolic and inflammatory signatures.

MeSH Terms

  • Adult
  • Biomarkers
  • Blood Pressure
  • C-Reactive Protein
  • Cardiovascular Diseases
  • Circadian Rhythm
  • Diet
  • Energy Intake
  • Fasting
  • Heart Rate
  • Humans
  • Inflammation
  • Male
  • Metabolic Diseases
  • Middle Aged
  • Nutritional Physiological Phenomena
  • Regression Analysis
  • Risk Factors
  • Young Adult

Keywords

  • Aging
  • Health benefits
  • Inflammation
  • Recurrent fasting


Characteristics of patients with rheumatoid arthritis undergoing primary total joint replacement: A 14-year trend analysis (2004-2017).

To examine time trends in the characteristics of patients with rheumatoid arthritis (RA) undergoing primary total joint replacement (TJR). Biologics were approved in Japan for use in patients with RA in July 2003. A total of 403 large joints in 282 patients who underwent TJR at our institute between 1 January 2004 and 31 December 2017 were retrospectively examined. A significant decreasing trend was observed in the number of TJRs performed from 2004 to 2017 ([i]p[/i] = 0.013). No significant trend was observed in time from RA onset to TJR ([i]p[/i] = 0.294). Age at RA onset ([i]p[/i] = 0.034) showed a significant increasing trend, and serum C-reactive protein (CRP) levels showed a significant decreasing trend ([i]p[/i] < 0.001). Negative CRP (defined as ≤0.3 mg/dl; partial regression coefficient ([i]B[/i]) = 2.44, [i]p[/i] = 0.016) was independently associated with time from RA onset to TJR as well as age at RA onset and juxta-articular osteophyte formation. The number of TJRs decreased since the approval of biologics in Japan, and changes were observed in the characteristics of patients with RA undergoing TJR. Negative CRP was an independent factor associated with longer time from RA onset to TJR.

MeSH Terms

  • Adult
  • Aged
  • Antirheumatic Agents
  • Arthritis, Rheumatoid
  • Arthroplasty, Replacement
  • Arthroplasty, Replacement, Knee
  • Biological Products
  • Drug Utilization
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Postoperative Complications

Keywords

  • C-reactive protein
  • Rheumatoid arthritis
  • aging
  • arthroplasty
  • drug therapy


Impact of C-reactive protein on osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells.

Medial vascular calcification occurs during the aging process and is strongly accelerated by chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels are associated with vascular calcification, cardiovascular events and mortality in CKD patients. CRP is an important promoter of vascular inflammation. Inflammatory processes are critically involved in initiation and progression of vascular calcification. Thus, the present study explored a possible impact of CRP on vascular calcification. We found that CRP promoted osteo-/chondrogenic transdifferentiation and aggravated phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of primary human aortic smooth muscle cells (HAoSMCs). These effects were paralleled by increased cellular oxidative stress and corresponding pro-calcific downstream-signaling. Antioxidants or p38 MAPK inhibition suppressed CRP-induced osteo-/chondrogenic signaling and mineralization. Furthermore, silencing of Fc fragment of IgG receptor IIa (FCGR2A) blunted the pro-calcific effects of CRP. Vascular CRP expression was increased in the klotho-hypomorphic mouse model of aging as well as in HAoSMCs during calcifying conditions. In conclusion, CRP augments osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells through mechanisms involving FCGR2A-dependent induction of oxidative stress. Thus, systemic inflammation may actively contribute to the progression of vascular calcification.

MeSH Terms

  • Aging
  • Animals
  • C-Reactive Protein
  • Cell Transdifferentiation
  • Cells, Cultured
  • Chondrogenesis
  • Disease Models, Animal
  • Glucuronidase
  • Humans
  • Mice
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Osteogenesis
  • Oxidative Stress
  • RNA, Small Interfering
  • Receptors, IgG
  • Renal Insufficiency, Chronic
  • Signal Transduction
  • Vascular Calcification

Keywords

  • CKD
  • CRP
  • osteo-/chondrogenic signaling
  • oxidative stress
  • vascular calcification
  • vascular smooth muscle cells


Inflammatory markers and bone health in postmenopausal women: a cross-sectional overview.

Cytokines, chemokines, C-reactive proteins (CRP) and ferritin are known inflammatory markers. However, cytokines such as interleukin (IL-1β), (IL-6) and tumour necrosis factor (TNF-α) have been reported to interfere with both the bone resorption and bone formation processes. Similarly, immune cell cytokines are known to contribute to inflammation of the adipose tissue especially with obesity. IL-10 but not IL-33 has been linked to lower ferritin levels and anemia. In this study, we hypothesized that specific cytokine levels in the plasma of women with low bone mineral density (BMD) would be higher than those in the plasma of healthy women due to the actions of elevated levels of pro-inflammatory cytokines in inducing osteoclast formation and differentiation during senescence. Levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in the plasma of the osteoporotic group compared to the osteopenic and/or healthy groups. Meanwhile CRP levels were significantly lower in women with osteoporosis ([i]P[/i] = 0.040) than the osteopenic and healthy groups. Hip BMD values were significantly lower in women with high/detectable values of IL-1β ([i]P[/i] = 0.020) and IL-6 ([i]P[/i] = 0.030) compared to women where these were not detected. Similarly, women with high/detectable values of IL-1β had significantly lower spine BMD than those where IL-1β was not detected ([i]P[/i] = 0.030). Participants' CRP levels were significantly positively correlated with BMI, fat mass and fat percentage ([i]P[/i] < 0.001). In addition, ferritin levels of women with high/detectable values of anti-osteoclastogenic IL-10 ([i]P[/i] = 0.012) and IL-33 ([i]P[/i] = 0.017) were significantly lower than those where these were not detected. There was no statistically significant association between TNF-α and BMD of the hip and lumbar spine. High levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and MCP-1 in apparently healthy postmenopausal women are associated with bone health issues. In addition, an increase in levels of IL-10 and IL-33 may be associated with low ferritin levels in this age group. ANZCTR, ACTRN12617000802303. Registered May 31st, 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373020.


Keywords

  • Aging
  • Bone health
  • Bone mineral density
  • Chemokines
  • Cytokines
  • Ferritin
  • Inflammatory markers
  • Osteo-immunology
  • Postmenopausal women


Frailty is associated with elevated CRP trajectories and higher numbers of neutrophils and monocytes.

With aging, the human immune system undergoes several changes. The clinical relevance of these changes, however, is relatively unknown. We investigated immunological aspects of human aging in relation to frailty in the Doetinchem Cohort Study (DCS). We calculated a frailty index score based on 36 health parameters for each individual in the DCS with data obtained in the period 2008-2016. The frailty index was used to define three health groups ('healthy', 'intermediate', and 'frail'), stratified by age and sex. In a subcohort (n = 289, 60-85 years, selected by balanced random sampling per frailty group), we collected blood samples between October 2016 and March 2017 to determine absolute numbers of leukocyte subsets. In addition, cytomegalovirus serostatus was assessed. C-reactive protein (CRP) levels were longitudinally assessed in four consecutive plasma samples per individual. These samples had been previously collected (1993-2013) as part of the DCS at regular time intervals and spanning a period of >15 years. We observed higher numbers of myeloid derived neutrophils and monocytes in the frail group compared to the healthy group in both men and women, and, retrospectively, consistently higher CRP concentrations over a period of >15 years. An increase in CRP concentration with age was found in women, but not in men. Frailty was not associated with cytomegalovirus serostatus or with changes in lymphoid derived T-, B-, or NK-cell numbers. Frail elderly, compared to their age- and sex-matched peers, endure a chronic and stable low-grade inflammation, which is associated with a myeloid cell lineage expansion. These findings could help to monitor clinically significant immunological decline in the elderly.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • C-Reactive Protein
  • Female
  • Frailty
  • Humans
  • Inflammation
  • Leukocyte Count
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sex Factors


Relationship between circulating microparticles and hypertension and other cardiac disease biomarkers in the elderly.

Microparticles are procoagulant membrane vesicles that play role in endothelium dysfunction pathogenesis and are increased in hypertension, acute/chronic vascular pathological events. Here; we aimed to compare MPs levels of hypertensive geriatric patients with healthy age-match-patients, discuss its availability as a cardiovascular biomarker and investigate its relationship with other inflammatory markers. Forty seven hypertensive geriatric patients (M/F;15/32) and 47 healthy controls (M/F;19/28) were included in the study. MPs levels were examined functionally through thrombin generation test (TGT) parameters (MPS Lag time, MPS ETP, MPs Peak, MPS start Tail) and compared with CRP, N/L ratio, ALT, GGT, thrombocyte parameters. Decrease in MPS Lag time, increase in MPS ETS and MPs Peak elevation were accepted as tendency to coagulation which meant an increase in number and function of MPs. No significant difference was found between 2 groups for MPS tests (MPS Lag time, MPS ETP, MPs Peak, MPS start Tail). Platelet count was significantly higher in hypertensive patient group. There was a negative correlation between age and MPs Peak, MPS Lag time. There was a positive correlation between CRP and MPS ETP, MPs Peak values. Our present findings might help to understand the hemostasis via TGT parameters, in the elderly. Contribution of MPs to thrombosis tendency seen with aging and increased number of circulating MPs caused by hypertensive endothelial dysfunction must be taken into consideration. MPs might be accepted as vascular inflammation and damage markers and used as follow up tools of medical treatment of vascular inflammation-related diseases.

MeSH Terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Biomarkers
  • Blood Platelets
  • Blood Pressure
  • Case-Control Studies
  • Cell-Derived Microparticles
  • Cross-Sectional Studies
  • Endothelium, Vascular
  • Female
  • Heart Diseases
  • Hemostasis
  • Humans
  • Hypertension
  • Inflammation Mediators
  • Male
  • Prognosis
  • Risk Assessment
  • Risk Factors

Keywords

  • Endothelial dysfunction
  • Hypertension in the elderly
  • Microparticles
  • Procoagulant activity
  • Thrombin generation test


The Impact of Prophylactic Lacosamide on LPS-Induced Neuroinflammation in Aged Rats.

Sepsis-induced central nervous system damage is called sepsis-associated encephalopathy (SAE). In addition to neuroinflammation, oxidative stress and apoptosis act in the development of SAE. In the current study, we evaluated the protective effects of lacosamide (LCM) on neuroinflammation induced by lipopolysaccharide (LPS). Twenty-four Wistar albino rats were divided into 3 groups as controls, LPS group (5 mg/kg i.p.), and LPS plus LCM group (5 mg/kg i.p and 40 mg/kg i.p, respectively). In the rat brain, LPS-induced tissue damage was revealed histopathologically as hyperemia and microhemorrhages. LCM pretreatment ameliorated these histopathological changes. LPS decreased brain TAS levels and significantly increased MDA, CRP, HSP, IL-1β, and TNF-α expressions in the cortex, hippocampus, and cerebellum. Western analysis revealed increased brain tissue levels of TNF-α, NF-Kβ, and caspase-3 following LPS. Prophylactic LCM treatment reversed these parameters including oxidative stress, inflammation, and apoptosis in the cortex, hippocampus, and cerebellum.

MeSH Terms

  • Aging
  • Animals
  • Apoptosis
  • Brain
  • Cerebellum
  • Cerebral Cortex
  • Hippocampus
  • Inflammation
  • Lacosamide
  • Lipopolysaccharides
  • Oxidative Stress
  • Premedication
  • Protective Agents
  • Rats
  • Sepsis-Associated Encephalopathy

Keywords

  • LPS
  • brain
  • lacosamide
  • neuroinflammation
  • oxidative stress
  • sepsis


Impaired sleep quality is associated with concurrent elevations in inflammatory markers: are post-menopausal women at greater risk?

Chronic inflammation and impaired sleep increase the risk for cardiovascular disease. Menopausal women may be particularly at risk as a result of impaired sleep. The objective of the current investigation was to assess the relationship between poor sleep and C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) in healthy non- and postmenopausal women and men. A fasting blood draw was obtained from 122 healthy men and women (31 were postmenopausal). Higher scores on the Pittsburgh Sleep Quality Index (PSQI) were used to define poor sleep. Given the sample size and healthy nature of the sample, hierarchical linear regression analyses were performed on a composite inflammatory score involving CRP, IL-6, and TNF-α. Sex/menopausal group and PSQI were entered as predictors, and the interaction of the group by PSQI was entered stepwise. Analyses on MPO were performed separately. Sleep quality was associated with higher inflammatory activity (β = 0.272, P = 0.003), which remained significant (P = 0.046) after controlling for age, waist circumference, exercise times per week, and depressive symptoms. While in the same direction, sleep quality was not significantly associated with MPO. Dichotomizing sleep quality led to similar results. Impaired sleep quality is independently associated with greater inflammation in healthy adult men and women. Despite an overall less favorable metabolic and inflammatory profile in postmenopausal women, impaired sleep did not emerge as differentially related to inflammatory activity in this group.

MeSH Terms

  • Adult
  • Aging
  • Biomarkers
  • C-Reactive Protein
  • Female
  • Humans
  • Inflammation
  • Interleukin-6
  • Male
  • Middle Aged
  • Peroxidase
  • Postmenopause
  • Premenopause
  • Sleep Wake Disorders
  • Tumor Necrosis Factor-alpha

Keywords

  • C-reactive protein
  • IL-6
  • Menopause
  • Sex
  • Sleep
  • TNF-α


A novel biomarker of cardiometabolic pathology in schizophrenia?

Persons with schizophrenia and schizoaffective disorder (PwS) have high rates of cardiometabolic pathology that contributes to premature mortality. Adiponectin is a metabolic hormone affecting insulin sensitivity and inflammation, and is active in the brain. High-molecular weight (HMW) adiponectin is considered a more sensitive marker of metabolic dysfunction than total adiponectin, but has been poorly studied in schizophrenia. This was a cross-sectional study of 100 PwS, age range 26-68 years (46 women), and 93 age- and sex-comparable non-psychiatric comparison (NC) subjects. Assessments included measures of psychopathology, physical health, cognitive function, and circulating biomarkers of metabolic dysfunction (HMW adiponectin, lipids, insulin resistance) and inflammation (high-sensitivity C-reactive protein or hs-CRP, Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10). HMW adiponectin levels were lower in PwS compared to NCs. Lower HMW adiponectin levels were associated with higher body mass index (BMI), higher Framingham risk for coronary heart disease, higher number of metabolic syndrome criteria, greater insulin resistance, lower HDL cholesterol, and higher hs-CRP in both groups. Only in PwS, lower HMW adiponectin correlated with younger age. In the best-fit regression models of HMW adiponectin, lower levels were associated with lower HDL cholesterol and minority race/ethnicity in both groups; but with younger age, non-smoking, higher insulin resistance, and a diagnosis of schizoaffective disorder only among PwS, and with male sex, better cognitive functioning, and higher hs-CRP levels in NCs only. HMW adiponectin may be a promising biomarker of cardiometabolic health, especially among PwS. Adiponectin is a potential target for lifestyle and pharmacological interventions. Research on the possible role of HMW adiponectin in modifying cardiometabolic pathology in schizophrenia is needed.

MeSH Terms

  • Adiponectin
  • Adult
  • Aged
  • Biomarkers
  • Cardiovascular Diseases
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Metabolic Syndrome
  • Middle Aged
  • Molecular Weight
  • Psychotic Disorders
  • Schizophrenia

Keywords

  • Adipokines
  • Aging
  • Body mass index
  • Cytokines
  • Hemoglobin A1C
  • Insulin resistance


Differential clusters of modifiable risk factors for impaired fasting glucose [i]versus[/i] impaired glucose tolerance in adults 50 years of age and older.

The aim of this study was to identify modifiable risk factors associated with isolated impaired fasting glucose (IFG), isolate impaired glucose tolerance (IGT), or combined IFG-IGT in men and women aged 50 years and older. Cross-sectional analyses were performed in 703 men and women aged between 50 and 80 years old from NHANES (2007-2008). Outcome variables: IFG and IGT (ADA 2003), estimated body composition, cardiometabolic profile, and socio-demographic, dietary, and lifestyle factors. First, 235 had normal glucose tolerance (men = 38.3%, women = 61.7%), 243 had IFG (men = 61.7%, women = 38.3%), 67 had IGT (men = 40.3%, women = 59.7%) and 158 had both conditions (men = 57.0%, women = 43.0%). The only common determinant of both IFG and IGT was triglyceride levels. High total fat mass index (FMI) and high total fat-free mass index (FFMI) were independently associated with IFG; while high C-reactive protein (CRP) levels were independently associated with IGT. Finally, combined IFG-IGT was associated with inadequate fiber intake, high FMI, FFMI, and CRP levels. Middle-age and older individuals presented different modifiable risk factors depending on whether they had IFG or IGT. IFG was associated with deteriorated body composition and lipids, whereas IGT was associated with deteriorated lipids and inflammatory factors. IFG-IGT, on the other hand, was associated with a larger number of risk factors, including worsen body composition, cardiometabolic and dietary factors. To prevent the transition to type 2 diabetes, specific clinical interventions targeting these risk factors should be considered.


Keywords

  • aging
  • combined IFG-IGT
  • prediabetes
  • risk factors


[Association of plasma albumin and hypersensitive C-reactive protein with 5-year all-cause mortality among Chinese older adults aged 65 and older from 8 longevity areas in China].

To investigate the relationship of plasma albumin and hypersensitive C-reactive protein (Hs-CRP) with 5-year all-cause mortality among Chinese older adults aged 65 and older. Data was collected in 8 longevity areas of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) study conducted by Chinese Center for Disease Control and Prevention and Peking University at baseline survey in 2012 and 2014, the participants enrolled in 2012 was followed-up in 2014 and 2017, the participants enrolled in 2014 was followed-up in 2017 only. Finally, 3 118 older adults aged 65 and older with complete information on albumin, Hs-CRP and body mass index (BMI) were included in this study. Plasma samples of older adults were collected for the detection of albumin and Hs-CRP at baseline survey. Survival status and follow-up time was recorded for all participants. All older adults were divided into 4 groups according to the levels of plasma albumin and Hs-CRP, and Cox proportional hazard models were constructed to assess their influence on the risk of all-cause mortality. Among 3 118 older adults included, the prevalence of hypoalbuminemia was 10.1% (316/3 118), and was 22.8% (711/3 118) for elevated Hs-CRP. During 10 132 person-years of follow-up, 1 212 participants died. Participants with hypoalbuminemia had increased risk of all-cause mortality, with an hazard ratio ([i]HR[/i]) and 95% confidential interval ([i]CI[/i]) of 1.18 (1.01-1.38), compared to participants with normal plasma albuminemia; participants with elevated Hs-CRP had increased risk of all-cause mortality, with an [i]HR[/i] (95[i]%CI[/i]) of 1.18 (1.04-1.35), compared to participants with normal plasma Hs-CRP. Participants with normal plasma albumin and elevated Hs-CRP, with hypoalbuminemia and normal Hs-CRP, with hypoalbuminemia and elevated Hs-CRP also had increased risk of all-cause mortality when compared to those with normal plasma albumin and normal Hs-CRP, the [i]HR[/i] (95[i]%CI[/i]) were 1.16 (1.01-1.34), 1.11 (0.91-1.37) and 1.43 (1.11-1.83), respectively. Hypoalbuminemia and elevated Hs-CRP were responsible for increased risk of 5-year all-cause mortality among Chinese older adults from 8 longevity areas.

MeSH Terms

  • Aged
  • Biomarkers
  • C-Reactive Protein
  • China
  • Humans
  • Longevity
  • Mortality
  • Risk Factors
  • Serum Albumin

Keywords

  • Albumin
  • Cohort studies
  • Hypersensitive C-reactive protein
  • Mortality risk
  • Older adults


[Estimated glomerular filtration rate and post-hospital mortality after discharge from an acute care for the elderly unit].

To determine the relationship between estimated glomerular filtration rate (eGFR) and mortality in a retrospective cohort of older adults admitted to an acute care for the elderly (ACE) unit. The study included 1,678 patients aged 60 years and over admitted to an AEC, in Cali, Colombia, from 2012 to 2015, and followed- up until 2016. The primary outcome was mortality. Renal function (eGFR) was estimated using Modification of Diet in Renal Disease Study (MDRD-4) equation. The renal function was grouped according to the eGFR (ml/min/1.73m ) as follows: slightly decreased (≥60), moderately decreased (30-59), and severely decreased (<30). Bivariate survival and multivariate Cox regression analyses were performed. In the univariate analysis, patients with severely decreased eGFR had higher mortality than those with a higher eGFR (P=.046). In the group with severely decreased eGFR, survival was lower in the functionally dependent group (Barthel index [IB]<60) than in the independent group (IB≥60) (log rank test; P=.001). In the multivariate analysis, there was a significant increase in the risk of death in the elderly with severely decreased eGFR (<30) compared with slightly decreased eGFR (≥60) (hazard ratio [HR], 1.44; 95% confidence interval [CI]; 1.02-2.05, P=.039). There was also a significant increase in the risk of death in the dependent elderly compared to the independent ones [HR 1.72; 95% CI; 1.26-2.34, P=.000], those who had the high morbidity (≥4) with low albumin (<3.2g/dL) compared with those with low morbidity (0-3) and high albumin (≥3.2) [HR 1.77; 95% CI; 1.18-2.65, P=.005], and in those with a high (16-102mg/dL) C-reactive protein (CRP) compared with those with low CRP (0-15) [HR 1.42; 95% CI; 1.01-2.01, P=.043]. The risk of mortality after hospital admission to an AEC unit is greater in patients with eGFR<30. Poor functional status performance, high comorbidity, low plasma albumin, and increased inflammation markers are additional prognostic factors to be taken into account. The improvement in the functional status could improve the survival after hospitalisation.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Critical Care
  • Female
  • Geriatrics
  • Glomerular Filtration Rate
  • Hospital Units
  • Humans
  • Male
  • Middle Aged
  • Mortality
  • Patient Discharge
  • Retrospective Studies

Keywords

  • Adultos mayores
  • Glomerular filtration rate
  • Hospital admission
  • Hospitalización
  • Mortalidad.
  • Mortality
  • Older adults
  • Tasa de filtración glomerular


Racial differences in inflammation and outcomes of aging among kidney transplant candidates.

Inflammation is more common among African Americans (AAs), and it is associated with frailty, poor physical performance, and mortality in community-dwelling older adults. Given the elevated inflammation levels among end-stage renal disease (ESRD) patients, inflammation may be associated with adverse health outcomes such as frailty, physical impairment, and poor health-related quality of life (HRQOL), and these associations may differ between AA and non-AA ESRD patients. One thousand three ESRD participants were recruited at kidney transplant evaluation (4/2014-5/2017), and inflammatory markers (interleukin-6 [IL-6], tumor necrosis factor-a receptor-1 [TNFR1], C-reactive protein [[[CRP]]]) were measured. We quantified the association with frailty (Fried phenotype), physical impairment (Short Physical Performance Battery [SPPB]), and fair/poor HRQOL at evaluation using adjusted modified Poisson regression and tested whether these associations differed by race (AA vs. non-AA). Non-AAs had lower levels of TNFR1 (9.7 ng/ml vs 14.0 ng/ml, p < 0.001) and inflammatory index (6.7 vs 6.8, p < 0.001) compared to AAs, but similar levels of IL-6 (4.5 pg/ml vs 4.3 pg/ml, p > 0.9) and CRP (4.7 μg/ml vs 4.9 μg/ml, p = 0.4). Non-AAs had an increased risk of frailty with elevated IL-6 (RR = 1.58, 95% CI:1.27-1.96, p < 0.001), TNFR1 (RR = 1.60, 95% CI:1.25-2.05, p < 0.001), CRP (RR = 1.41, 95% CI:1.10-1.82, p < 0.01), and inflammatory index (RR = 1.82, 95% CI:1.44-2.31, p < 0.001). The associations between elevated inflammatory markers and frailty were not present among AAs. Similar results were seen with SPPB impairment and poor/fair HRQOL. Non-AAs with elevated inflammatory markers may need closer follow-up and may benefit from prehabilitation to improve physical function, reduce frailty burden, and improve quality of life prior to transplant.

MeSH Terms

  • Adult
  • African Americans
  • Aged
  • Aging
  • Biomarkers
  • Cohort Studies
  • Continental Population Groups
  • Cross-Sectional Studies
  • Female
  • Frailty
  • Humans
  • Inflammation
  • Inflammation Mediators
  • Kidney Failure, Chronic
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Prospective Studies
  • Quality of Life
  • Treatment Outcome

Keywords

  • End-stage renal disease
  • Frailty
  • HRQOL
  • Inflammation
  • Race

{{medline-entry |title=Is anger, but not sadness, associated with chronic inflammation and illness in older adulthood? |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31070399 |abstract=The discrete emotion theory of affective aging postulates that anger, but not sadness, becomes increasingly maladaptive during older adulthood in predicting health-relevant physiological processes and chronic disease (Kunzmann