LPA
Apolipoprotein(a) precursor (EC 3.4.21.-) (Apo(a)) (Lp(a))
PublicationsПравить
A dramatic increase in aging populations and low birth rates rapidly drive aging societies and increase aging-associated neurodegenerative diseases. However, functional food or medicinal formulations to prevent geriatric brain disorders are not readily available. [i]Panax ginseng[/i] is a candidate, since ginseng has long-been consumed as a rejuvenating agent. However, the underlying molecular mechanisms and the components of ginseng that are responsible for brain rejuvenation and human longevity are unknown. Accumulating evidence shows that gintonin is a candidate for the anti-aging ingredient of ginseng, especially in brain senescence. Gintonin, a glycolipoprotein complex, contains three lipid-derived G protein-coupled receptor ligands: lysophosphatidic acids (LPAs), lysophosphatidylinositols (LPIs), and linoleic acid (LA). LPA, LPI, and LA act on six LPA receptor subtypes, GPR55, and GPR40, respectively. These G protein-coupled receptors are distributed within the nervous and non-nervous systems of the human body. Gintonin-enriched fraction (GEF) exhibits anti-brain senescence and effects against disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Oral administration of gintonin in animal models of d-galactose-induced brain aging, AD, HD, and PD restored cognitive and motor functions. The underlying molecular mechanisms of gintonin-mediated anti-brain aging and anti-neurodegenerative diseases include neurogenesis, autophagy stimulation, anti-apoptosis, anti-oxidative stress, and anti-inflammatory activities. This review describes the characteristics of gintonin and GEF, and how gintonin exerts its effects on brain aging and brain associated-neurodegenerative diseases. Finally, we describe how GEF can be applied to improve the quality of life of senior citizens in aging societies.
Keywords
- Brain aging
- Gintonin
- Neurodegenerative diseases
- Panax ginseng
- Rejuvenation
With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance and physical frailty. A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis (LPA) was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout and mortality at two-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty. An LPA model with 5 classes best described the data, yielding two subgroups suffering from pure depression ('mild' and 'severe' depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labelled as 'amnestic depression', 'frail-depressed, physically dominated' and 'frail-depressed, cognitively dominated'. The prospective analyses showed that patients in the subgroup of "mild depression" and "amnestic depression" had the highest remission rates, while patients in both frail-depressed subgroups had the highest mortality rates. Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy and augmentation with geriatric rehabilitation.
Keywords
- cognitive aging
- depression
- frailty
Older adults have the highest sedentary time across all age groups, and only a small portion is meeting the minimum recommendations for weekly physical activity. Little research to date has looked at how changes in one of these behaviours influences the other. To assess changes in 24-h movement behaviours (sedentary time, light intensity physical activity (LPA), moderate-vigorous PA (MVPA) and sleep) over three consecutive days, following acute bouts of exercise of varying intensity in older adults. Participants (n = 28, 69.7 ± 6.5 years) completed a maximal exercise test and the following exercise protocols in random order: moderate continuous exercise (MOD), high-intensity interval exercise (HI) and sprint interval exercise (SPRT). A thigh-worn device (ActivPAL™) was used to measure movement behaviours at baseline and the 3 days following each exercise session. Repeated measures analysis of variance indicated that compared to baseline, participants decreased MVPA in the 3 days following all exercise sessions and decreased LPA following HI and SPRT (p < 0.05). Over half of the sample had clinically meaningful increases in sedentary time (30 min/day) in the days following exercise participation. Older adults who compensate for exercise participation by reducing physical activity and increasing sedentary time in subsequent days may require behavioural counseling to ensure that incidental and recreational physical activities are not reduced. It appears that older adults compensate for acute exercise by decreasing MVPA and LPA, and increasing sedentary time in the days following exercise. Future research is needed to determine whether compensation persists with regular engagement.
MeSH Terms
- Accelerometry
- Aged
- Exercise
- Exercise Test
- Humans
- Sedentary Behavior
- Sleep
Keywords
- Aging
- Compensation
- High intensity
- Movement behaviours
Elevated lipoprotein(a) (Lp[a]) levels are associated with atherosclerotic cardiovascular diseases. The association between high Lp(a) levels and human longevity phenotypes is, however, controversial. To examine whether genetically determined Lp(a) levels are associated with parental life span and chronic disease-free survival (health span) and the association between Lp(a) levels and long-term, all-cause mortality risk. In this genetic association study, cross-sectional mendelian randomization (UK Biobank [2006-2010] and LifeGen Consortium) and prospective analyses (European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk [1993-1997, with patients followed up to 2016]) were conducted using individual-level data on 139 362 participants. The association between a weighted genetic risk score of 26 independent single-nucleotide polymorphisms at the LPA locus on parental life span using individual participant data from the UK Biobank, as well as with summary statistics of a genome-wide association study of more than 1 million life spans (UK Biobank and LifeGen), were examined. The association between these single-nucleotide polymorphisms and the age at the end of the health span was tested using summary statistics of a previous genome-wide association study in the UK Biobank. The association between Lp(a) levels and all-cause mortality in the EPIC-Norfolk study was also investigated. Data were analyzed from December 2018 to December 2019. Genetically determined and measured Lp(a) levels. Parental life span, health span, and all-cause mortality. In 139 362 white British participants (mean [SD] age, 62.8 [3.9] years; 52% women) from the UK Biobank, increases in the genetic risk score (weighted for a 50-mg/dL increase in Lp[a] levels) were inversely associated with a high parental life span (odds ratio, 0.92; 95% CI, 0.89-0.94; P = 2.7 × 10-8). Using the Egger-mendelian randomization method, a negative association between LPA single-nucleotide polymorphisms and parental life span (mean [SD] Egger-mendelian randomization slope, -0.0019 [0.0002]; P = 2.22 × 10-18) and health span (-0.0019 [0.0003]; P = 3.00 × 10-13) was noted. In 18 720 participants from EPIC-Norfolk (5686 cases), the mortality risk for those with Lp(a) levels equal to or above the 95th percentile was equivalent to being 1.5 years older in chronologic age (β coefficient [SE], 0.194 [0.064]). The results of this study suggest a potential causal effect of absolute Lp(a) levels on human longevity as defined by parental life span, health span, and all-cause mortality. The results also provide a rationale for trials of Lp(a)-lowering therapy in individuals with high Lp(a) levels.
MeSH Terms
- Aged
- Case-Control Studies
- Cross-Sectional Studies
- Female
- Humans
- Lipoprotein(a)
- Longevity
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Parents
- Phenotype
- Prospective Studies
- Risk Factors
Circulating autotaxin (ATX) is elevated in persons with liver disease, particularly in the setting of chronic hepatitis C virus (HCV) and HCV/HIV infection. It is thought that plasma ATX levels are, in part, attributable to impaired liver clearance that is secondary to fibrotic liver disease. In a discovery data set, we identified plasma ATX to be associated with parameters of systemic immune activation during chronic HCV and HCV/HIV infection. We and others have observed a partial normalization of ATX levels within months of starting interferon-free direct-acting antiviral (DAA) HCV therapy, consistent with a non-fibrotic liver disease contribution to elevated ATX levels, or HCV-mediated hepatocyte activation. Relationships between ATX, lysophosphatidic acid (LPA) and parameters of systemic immune activation will be discussed in the context of HCV infection, age, immune health, liver health, and hepatocellular carcinoma (HCC).
Keywords
- Aging
- Autotaxin
- Hepatitis
- Hepatocellular Carcinoma
- Immune Activation
- Immunity
- Inflammation
- Liver
- Lysophosphatidic Acid
Hutchinson-Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin, resulting in premature aging. HGPS cells show morphological abnormalities of the nuclear membrane, reduced cell proliferation rates, accumulation of reactive oxygen species (ROS), and expression of senescence markers. Lysophosphatidic acid (LPA) is a growth factor-like lipid mediator that regulates various physiological functions via activating multiple LPA G protein-coupled receptors. Here, we study the roles of LPA and LPA receptors in premature aging. We report that the protein level of LPA was highly downregulated through internalization and the lysosomal degradation pathway in Progerin-transfected HEK293 cells. By treating Progerin HEK293 cells with an LPA agonist (OMPT, 1-Oleoyl-2-O-methyl-rac-glycerophosphothionate) and performing shRNA knockdown of the Lpa3r transcript in these cells, we showed that LPA activation increased expression levels of antioxidant enzymes, consequently inhibiting ROS accumulation and ameliorating cell senescence. LPA was shown to be downregulated in HGPS patient fibroblasts through the lysosomal pathway, and it was shown to be crucial for ameliorating ROS accumulation and cell senescence in fibroblasts. Moreover, in a zebrafish model, LPA deficiency was sufficient to cause premature aging phenotypes in multiple organs, as well as a shorter lifespan. Taken together, these findings identify the decline of LPA as a key contributor to the premature aging phenotypes of HGPS cells and zebrafish.
Keywords
- 1-Oleoyl-2-O-methyl-rac-glycerophosphothionate
- Hutchinson-Gilford progeria syndrome
- LPA3
- cell senescence
- lysophosphatidic acid
- reactive oxygen species
Physical activity can help to protect against cognitive decline in older adults. However, little is known about the potential combined relationships of time spent in sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with indices of cognitive health. We examined the cross-sectional associations of objectively-determined sedentary and physically-active behaviors with an indicator of cognitive function decline (CFD) in older adults. A randomly-recruited sample of 511 Japanese older adults (47% male; aged 65-84 years) wore a tri-axial accelerometer for 7 consecutive days in 2017. Cognitive function was assessed by interviewers using the Japanese version of Mini-Mental State Examination, with a score of ≤23 indicating CFD. Associations of sedentary and physically-active behaviors with CFD were examined using a compositional logistic regression analysis based on isometric log-ratio transformations of time use, adjusting for potential confounders. Forty one (9.4%) of the participants had an indication of CFD. Activity compositions differed significantly between CFD and normal cognitive function (NCF); the proportion of time spent in MVPA was 39.1% lower, relative to the overall mean composition in those with CFD, and was 5.3% higher in those with NCF. There was a significant beneficial association of having a higher proportion of MVPA relative to other activities with CFD. LPA and SB were not associated with CFD when models were corrected for time spent in all activity behaviors. Larger relative contribution of MVPA was favorably associated with an indicator of CFD in older adults.
Keywords
- accelerometry
- aging
- exercise
- neurocognitive disorders
- sedentary lifestyle
White matter hyperintensities (WMH) are a common imaging finding indicative of cerebral small vessel disease. Lesion segmentation algorithms have been developed to overcome issues arising from visual rating scales. In this study, we evaluated two automated methods and compared them to visual and manual segmentation to determine the most robust algorithm provided by the open-source Lesion Segmentation Toolbox (LST). We compared WMH data from visual ratings (Scheltens' scale) with those derived from algorithms provided within LST. We then compared spatial and volumetric WMH data derived from manually-delineated lesion maps with WMH data and lesion maps provided by the LST algorithms. We identified optimal initial thresholds for algorithms provided by LST compared with visual ratings (Lesion Growth Algorithm (LGA): initial κ and lesion probability thresholds, 0.5; Lesion Probability Algorithm (LPA) lesion probability threshold, 0.65). LGA was found to perform better then LPA compared with manual segmentation. LGA appeared to be the most suitable algorithm for quantifying WMH in relation to cerebral small vessel disease, compared with Scheltens' score and manual segmentation. LGA offers a user-friendly, effective WMH segmentation method in the research environment.
Keywords
- White matter hyperintensity
- brain aging
- cerebral small vessel disease
- lesion segmentation
- methodology
- validation
Ageing is a life-long process characterized by a progressive loss of physical fitness compromising strength, flexibility, and agility. The purpose of this study was to use accelerometry to examine the relationship between sedentary time, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) with the elderly's physical fitness. Additionally, we aimed to examine the association between the aforementioned variables on older adults who fulfilled global recommendations on physical activity for health and on those who did not fulfil these recommendations. Eighty-three elderly (mean ± SD: 72.14 ± 5.61 years old) of both genders volunteered to participate in this cross-sectional study, being divided into an active group (n = 53; 71.02 ± 5.27 years old) and an inactive group (n = 30; 74.13 ± 5.72 years old) according to the established guidelines. Sedentary and physical activity times were assessed using an ActiGraph GT1M accelerometer, whereas physical fitness was evaluated with the Senior Fitness Test. MVPA time was correlated with lower body mass index (BMI) ((r = -0.218; [i]p[/i] = 0.048; -0.3 < r ≤ -0.1 (small)) and shorter time to complete the agility test ((r = -0.367; [i]p[/i] = 0.001; -0.5 < r ≤ -0.3 (low)). Moreover, MVPA time was positively correlated with aerobic endurance ((r = 0.397; [i]p[/i] = 0.000; 0.5 < r ≤ 0.3 (low)) and strength ((r = 0.243; [i]p[/i] = 0.027; 0.3 < r ≤ 0.1 (small)). In the inactive group, MVPA time was positively correlated with upper limb flexibility ((rs = 0.400; [i]p[/i] = 0.028; 0.5 < r ≤ 0.3 (low)); moreover, sedentary time was negatively correlated with upper limb flexibility ((r = -0.443; [i]p[/i] = 0.014; -0.5 < r ≤ -0.3 (low)), and LPA time was negatively correlated with BMI ((r = -0.423; [i]p[/i] = 0.020; -0.5 < r ≤ -0.3 (low)). In the active group, MVPA time was correlated with lower BMI ((rs = -0.320; [i]p[/i] = 0.020; -0.5 < r ≤ -0.3 (low)), and shorter time to complete agility test ((rs = -0.296; [i]p[/i] = 0.031; -0.3 < r ≤ -0.1 (small)). Our results reinforce the importance of promoting MVPA practice among the elderly, thereby allowing physical fitness maintenance or improvement.
MeSH Terms
- Accelerometry
- Aged
- Aged, 80 and over
- Aging
- Body Mass Index
- Cross-Sectional Studies
- Exercise
- Female
- Humans
- Male
- Physical Fitness
- Sedentary Behavior
Keywords
- accelerometry
- ageing
- health
- physical fitness
- sedentary behaviour
Studies show that regular moderate to vigorous physical activity is associated with a lower risk of cardiovascular disease, certain cancers, and premature death, but few studies have examined associations of light-intensity physical activity (LPA) and mortality, especially among older adults. The aim of this study was to investigate the association of LPA with the risks of death from all causes, cancer, cardiovascular diseases, and respiratory diseases among older adults in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Analyses included 123,232 participants in CPS-II NC, among whom 46,829 died during follow-up (1993-2014). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for self-reported leisure time LPA associated with mortality. Engaging in little or no LPA (<3 metabolic equivalent [[[MET]]]-h/week) was associated with a 16% higher risk of all-cause mortality (HR 1.16, 95% CI 1.12-1.20) compared to engaging in some LPA (3 to <9 MET-h/week) after adjusting for moderate to vigorous physical activity. However, there was no evidence of a dose-response relationship. A statistically significant interaction with age suggested that more LPA was associated with a lower risk of respiratory disease mortality only among participants aged ≥70 years (21 vs. 3 to <9 MET-h/week, HR 0.78, 95% CI 0.66-0.91; pint = 0.003). In this prospective study of older adults, accumulating little/no leisure time LPA was associated with a higher risk of mortality. It is of substantial public health value to demonstrate the potential benefits of engaging in any activity, even if light in intensity, among older adults given the aging US population.
MeSH Terms
- Aged
- Cardiovascular Diseases
- Cohort Studies
- Exercise
- Female
- Follow-Up Studies
- Humans
- Leisure Activities
- Male
- Middle Aged
- Mortality
- Neoplasms
- Proportional Hazards Models
- Prospective Studies
- Respiratory Tract Diseases
- Risk Factors
- Surveys and Questionnaires
- United States
Keywords
- Aging
- Cancer prevention study
- Leisure time physical activity
- Light-intensity physical activity
The aim of this study was to determine the relationship between bone mass (BM) and physical activity (PA) and sedentary behavior (SB) according to frailty status and sex using compositional data analysis. We analyzed 871 older people with an adequate nutritional status. Fried criteria were used to classify by frailty status. Time spent in SB, light intensity PA (LPA) and moderate-to-vigorous intensity PA (MVPA) was assessed from accelerometry for 7 days. BM was determined by dual-energy X-ray absorptiometry (DXA). The combined effect of PA and SB was significantly associated with BM in robust men and women ([i]p[/i] ≤ 0.05). In relation to the other behaviors, SB was negatively associated with BM in robust men while BM was positively associated with SB and negatively with LPA and MVPA in robust women. Moreover, LPA also was positively associated with arm BM ([i]p[/i] ≤ 0.01). Finally, in pre-frail women, BM was positively associated with MVPA. In our sample, to decrease SB could be a good strategy to improve BM in robust men. In contrast, in pre-frail women, MVPA may be an important factor to consider regarding bone health.
MeSH Terms
- Aged
- Aged, 80 and over
- Body Composition
- Bone Density
- Cross-Sectional Studies
- Exercise
- Female
- Frailty
- Humans
- Male
- Nutritional Status
Keywords
- aging
- bone mineral density
- light physical activity
- moderate-to-vigorous physical activity
- sedentary time
Physical activity (PA) is considered the best nonpharmacological treatment for the decrease in bone mass (BM) produced during aging. Therefore, it is essential to assess how the time spent in PA is distributed to control further changes. This work examines the relationship between movement behaviors and BM during aging, using compositional data analysis. We studied 227 older people 65 to 94 yr old (102 men and 125 women), divided by sex and bone status, over a period of 4 yr. Time spent in sedentary behavior (SB), light PA (LPA), and moderate to vigorous PA (MVPA), was assessed using accelerometry. BM was determined by dual-energy x-ray absorptiometry. The changes in MVPA were positively associated with the rate of BM decay at spine and leg in the whole sample and men's subgroup (P ≤ 0.05). In women, the rate of BM decay at spine and Ward's triangle were negatively associated with SB changes, and BM decay at femoral neck and Ward's triangle were positively associated with LPA (P ≤ 0.05). Increasing MVPA related to other movement behaviors produces improvements in the rate of bone change in older men, whereas to increase LPA and maintain MVPA would be the best approach to enhance BM in older women.
MeSH Terms
- Absorptiometry, Photon
- Accelerometry
- Aged
- Aged, 80 and over
- Aging
- Body Mass Index
- Bone Density
- Data Interpretation, Statistical
- Exercise
- Female
- Humans
- Longitudinal Studies
- Male
- Movement
- Osteoporosis
- Sedentary Behavior
- Sex Factors
Older adults spend 30% of their day in light-intensity physical activity (LPA). This study was designed to determine if increasing the proportion of time spent in LPA would affect glucose control. Older adults (N = 9) completed four 3-hour treatment conditions consisting of a seated control and 3 randomized conditions: (1) 20% time spent in continuous LPA, 80% seated; (2) 40% time spent in continuous LPA, 60% seated; and (3) 60% time spent in continuous LPA, 40% seated. Energy expenditure was measured continuously, and glucose was measured prior to mixed-meal ingestion and hourly thereafter. Glucose area under the curve was compared between conditions using Friedman test. There was a significant difference in glucose area under the curve by time spent in LPA (P < .001); specifically, between the seated and 60% LPA (mean difference = 35.0 [24.6] mg/dL, P = .01), seated and 40% LPA (mean difference = 25.2 [11.8] mg/dL, P = .03), seated and 20% LPA (mean difference = 17.8 [22.5] mg/dL, P = .03), 20% LPA and 60% LPA (mean difference = 17.2 [22.5] mg/dL, P = .01), and 40% LPA and 60% LPA (mean difference = 9.8 [7.3] mg/dL, P = .01). These results provide experimental evidence to the importance LPA has on metabolic health. If older adults who already spend, on average, about 3 hours per day in LPA, further increase their LPA, they could see benefit to glucose control.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Blood Glucose
- Energy Metabolism
- Exercise
- Female
- Humans
- Male
- Postprandial Period
Keywords
- aging
- exercise
- medicine
- physical activity prescription
- prevention
To examine the level of physical activity and sedentary behavior (SB), measured with accelerometers, in older adults from a city in southern Brazil according to sociodemographic and health characteristics. The sample consisted of 425 older adults (≥63 y) from the EpiFloripa Aging Study. Light physical activity (LPA), moderate to vigorous physical activity (MVPA), and SB were measured with accelerometers over a period of 7 days. The older adults spent two-thirds of the time of use in SB, one-third in LPA, and only 2.1% (95% confidence interval, 1.8-2.2) in MVPA. In the final adjusted model, lower levels of MVPA were observed for women, as well as higher SB and lower LPA and MVPA for those with higher age. There were also trends toward prolonged SB and lower LPA when participants had a higher educational level and toward lower MVPA with higher body mass index. Constant monitoring of physical activity levels and SB using objective measures is recommended and interventions should be directed at the groups most exposed to excessive SB and low levels of MVPA.
MeSH Terms
- Accelerometry
- Aged
- Aged, 80 and over
- Body Mass Index
- Brazil
- Cross-Sectional Studies
- Exercise
- Female
- Humans
- Male
- Middle Aged
- Sedentary Behavior
Keywords
- aging
- epidemiology
- objective measurement
Fear of falling (FoF) is common in older adults. Physical activity decreases as FoF increases. However, this association between physical activity and FoF may vary depending on activity intensity. The current study was performed to explore the associations between FoF and step count, light-intensity physical activity (LPA), and moderate/vigorous-intensity physical activity (MVPA) in community-dwelling older adults. This cross-sectional observational study was held at a local community association center, with 242 older adults living independently in the community (mean age: 75.1 ± 5.4 years). FoF was defined using the Falls Efficacy Scale-International and categorized into three levels (low, moderate, and high). Physical activity was measured using a uniaxial accelerometer worn for 7 consecutive days, and by calculating daily step count, LPA, and MVPA, over this period. Step count and physical activity intensity showed significant linear trends across FoF severity (p < .01, respectively). High FoF decreased step count by approximately 2,000 steps/day. Further, high FoF was significantly associated with short durations of both LPA and MVPA. In addition, moderate FoF was associated with decreased LPA duration, even after adjustment for confounding variables. Physical activity decreased concomitantly with a rise in FoF severity. Moreover, the association between physical activity and FoF differed by physical activity intensity level in community-dwelling older adults. Further studies are needed to investigate the causal relationship between FoF and objective physical activity in this population.
Keywords
- Fall and mobility problems
- Fear of falling
- Health promotion
- Physical fitness
- Successful aging
Ginseng has been used to improve brain function and increase longevity. However, little is known about the ingredients of ginseng and molecular mechanisms of its anti-brain aging effects. Gintonin is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand; LPA and LPA1 receptors are involved in adult hippocampal neurogenesis. D-galactose (D-gal) is used to induce brain -aging in animal models because long-term treatment with D-gal facilitates hippocampal aging in experimental adult animals by decreasing hippocampal neurogenesis and inducing learning and memory dysfunction. To investigate the protective effects of gintonin on D-gal-induced hippocampal senescence, impairment of long-term potentiation (LTP), and memory dysfunction. Brain hippocampal aging was induced by D-gal administration (150 mg/kg/day, s.c.; 10 weeks). From the 7th week, gintonin (50 or 100 mg/kg/day, per os) was co-administered with D-gal for 4 weeks. We performed histological analyses, LTP measurements, and object location test. Co-administration of gintonin ameliorated D-gal-induced reductions in hippocampal Ki67-immunoreactive proliferating cells, doublecortin-immunoreactive neuroblasts, 5-bromo-2'-deoxyuridine-incorporating NeuN-immunoreactive mature neurons, and LPA1 receptor expression. Co-administration of gintonin in D-gal-treated mice increased the expression of phosphorylated cyclic adenosine monophosphate response element binding protein in the hippocampal dentate gyrus. In addition, co-administration of gintonin in D-gal-treated mice enhanced LTP and restored the cognitive functions compared with those in mice treated with D-gal only. These results show that gintonin administration restores D-gal-induced memory deficits by enhancing hippocampal LPA1 receptor expression, LTP, and neurogenesis. Finally, the present study shows that gintonin exerts anti-brain aging effects that are responsible for alleviating brain aging-related dysfunction.
MeSH Terms
- Animals
- Cellular Senescence
- Disease Models, Animal
- Galactose
- Glycoproteins
- Hippocampus
- Long-Term Potentiation
- Lysophospholipids
- Memory Disorders
- Mice
- Neurogenesis
- Neurons
- Plant Extracts
- Receptors, Lysophosphatidic Acid
- Treatment Outcome
Keywords
- Anti-brain aging
- Brain senescence
- D-galactose
- Ginseng
- Gintonin
- Hippocampus
- Neurogenesis
Older adults have twice as many disabilities and four times as many physical limitations as people <60 years of age. Positive influence of physical activity to prevent these limitations has been presented in some studies. However, the indispensable combination of physical abilities and body composition parameters to maintain independence in later life and their relationship with physical activity has not been studied thoroughly. The main aim of this study was to determine possible differences in body composition and mobility parameters among older women with various levels of engagement in physical activity. In addition, the relationships between mobility and distinct levels of physical activity were evaluated in healthy older women. Eighty-one healthy older women aged from 65 to 91 years participated in this study and were allocated to three groups according to weekly moderate-to-vigorous physical activity (MVPA) time in 10 min bouts: highest MVPA (H-MVPA) (n = 27), middle MVPA (M-MVPA) (n = 40) and lowest MVPA (L-MVPA) (n = 14). Body composition (fat mass [FM] and fat free mass [FFM]) variables were assessed with dual-energy X-ray absorptiometry (DXA), objective physical activity data were collected with accelerometers and mobility tests were carried out to assess static and dynamic balance, lower limbs strength and aerobic capacity. No differences in body composition parameters were observed between studied groups (p > 0.0025). Women in L-MVPA covered significantly shorter distance during the six-minute walk test (6MWT) compared to H-MVPA (p = 0.000) and M-MVPA (p = 0.003) groups, performed timed-up-and-go (TUG) slower compared to H-MVPA group (p = 0.003) and five-times-sit-to-stand (FTSTS) test slower compared to H-MVPA (p = 0.006) and M-MVPA (p = 0.009) groups. There were no differences in body composition and mobility parameters between women in H-MVPA and M-MVPA groups. Regardless of bout duration, MVPA was correlated with mobility (TUG r = -0.47; FTSTS r = -0.37; 6MWT r = 0.53) parameters, whereas no relationships was observed with light physical activity (LPA). MVPA is associated with body composition and mobility parameters, while LPA is not related to any measured body composition nor mobility parameters. Accordingly, healthy older women could benefit from MVPA to maintain body composition and mobility parameters to preserve independence in later life.
MeSH Terms
- Absorptiometry, Photon
- Aged
- Aged, 80 and over
- Body Composition
- Body Mass Index
- Exercise
- Exercise Test
- Female
- Healthy Aging
- Healthy Volunteers
- Humans
- Linear Models
- Physical Functional Performance
Keywords
- Accelerometer
- Body mass index
- Healthy aging
- Mobility
- Moderate-to-vigorous physical activity
The effects of replacing sedentary time with light or moderate- to vigorous-intensity physical activity on frailty are not well known. To examine the mutually independent associations of sedentary time (ST), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with frailty status in older adults. A total of 628 people aged ≥65 years from the Toledo Study of Healthy Aging (TSHA) participated in this cross-sectional study. Frailty was measured using the Frailty Trait Scale. Hip-worn accelerometers were used to capture objective measurements of ST, LPA, and MVPA. Linear regression and isotemporal substitution analyses were used to examine associations of ST, LPA, and MVPA with frailty status. Analyses were also stratified by comorbidity. In single and partition models, LPA and MVPA were negatively associated with frailty. Time in sedentary behavior was not associated with frailty in these models. In the isotemporal substitution models, replacing 30 minutes/d of ST with MVPA was associated with a decrease in frailty [β -2.460; 95% confidence interval (CI): -3.782, -1.139]. In contrast, replacing ST with LPA was not associated with favorable effects on this outcome. However, when the models were stratified by comorbidity, replacing ST with MVPA had the greatest effect on frailty in both the comorbidity (β -2.556; 95% CI: -4.451, -0.661) and the no comorbidity group (β -2.535; 95% CI: -4.343, -0.726). Moreover, the favorable effects of LPA in people with comorbidities was found when replacing 30 minutes/d of ST with LPA (β -0.568; 95% CI: -1.050, -0.086). Substituting ST with MVPA is associated with theoretical positive effects on frailty. People with comorbidity may also benefit from replacing ST with LPA, which may have important clinical implications in order to decrease the levels of physical frailty.
MeSH Terms
- Accelerometry
- Aged
- Exercise
- Female
- Frailty
- Humans
- Male
- Sedentary Behavior
- Spain
Keywords
- Accelerometry
- aging
- comorbidity
- elderly
- exercise
- sedentary behavior
Frailty has been associated with worse outcomes in older trauma patients. Specifically, the utility of lean cross-sectional psoas muscle area (LPA) was examined as a potentially simple objective measure of frailty. Five hundred and fifty-four patients over the age of 65 were admitted with trauma between 2011 and 2014. Two hundred and twenty-five of these had adequate computed tomography imaging available for analysis. Cross-sectional area of the psoas muscle at the inferior endplate of L4 was quantified. Multivariate regression analysis showed no significant correlation between LPA and outcomes of mortality (P = 0.82) or inpatient complications (P = 0.22). Injury Severity Score (ISS) had a strong association with both mortality (odds ratio (OR) 9.5; 95% confidence interval (CI) 2.9-30.9) and inpatient complications (OR 9.9; 95% CI 3.5-27.7). Age also had an association with mortality (OR 1.09; 95% CI 1.03-1.16) and inpatient complications (OR 1.06; 95% CI 1.01-1.12). Lean psoas area was not an independent predictor of mortality or complications in a cohort of injured older patients.
MeSH Terms
- Aged
- Aging
- Body Composition
- Chi-Square Distribution
- Cross-Sectional Studies
- Female
- Frail Elderly
- Frailty
- Geriatric Assessment
- Humans
- Injury Severity Score
- Logistic Models
- Male
- Multivariate Analysis
- Odds Ratio
- Predictive Value of Tests
- Psoas Muscles
- Retrospective Studies
- Risk Factors
- Tomography, X-Ray Computed
- Wounds and Injuries
Keywords
- geriatric trauma
- lean psoas muscle
- outcome
- prognosis
- sarcopenia
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.
MeSH Terms
- Alleles
- Body Mass Index
- Coronary Disease
- Education
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- HLA-DQ alpha-Chains
- HLA-DRB1 Chains
- Humans
- Insulin Resistance
- Life Style
- Lipoprotein(a)
- Lipoproteins, HDL
- Longevity
- Lung Neoplasms
- Obesity
- Polymorphism, Single Nucleotide
- Smoking
- Socioeconomic Factors
Chronic stress affects health and the quality of life, with its effects being particularly relevant in ageing due to the psychobiological characteristics of this population. However, while some people develop psychiatric disorders, especially depression, others seem very capable of dealing with adversity. There is no doubt that along with the identification of neurobiological mechanisms involved in developing depression, discovering which factors are involved in positive adaptation under circumstances of extreme difficulty will be crucial for promoting resilience. Here, we review recent work in our laboratory, using an animal model lacking the LPA1 receptor, together with pharmacological studies and clinical evidence for the possible participation of the LPA1 receptor in mood and resilience to stress. Substantial evidence has shown that the LPA1 receptor is involved in emotional regulation and in coping responses to chronic stress, which, if dysfunctional, may induce vulnerability to stress and predisposition to the development of depression. Given that there is commonality of mechanisms between those involved in negative consequences of stress and in ageing, this is not surprising, considering that the LPA1 receptor may be involved in coping with adversity during ageing. Alterations in this receptor may be a susceptibility factor for the presence of depression and cognitive deficits in the elderly population. However, because this is only a promising hypothesis based on previous data, future studies should focus on the involvement of the LPA-LPA1 pathway in coping with stress and resilience in ageing.
MeSH Terms
- Aging
- Animals
- Brain
- Depression
- Humans
- Lysophospholipids
- Receptors, Lysophosphatidic Acid
- Resilience, Psychological
- Stress, Psychological
Keywords
- LPA-LPA1 pathway receptor
- LPA1 receptor
- ageing
- limbic system
- resilience
- stress
Aging is a risk factor of age-related diseases. With the increasing number of patients, serious consequences, and heavy economic burden, demands for drugs used to treat agerelated diseases have increased. As such, anti-aging substances should be isolated to develop drugs for the prevention and treatment of age-related diseases. In this study, a methanol extract of immature Arabidopsis thaliana seeds with coat was separated by using a K6001 yeast bioassay system. In order to investigate the action mechanism, four mutants, namely, Δuth1, Δskn7, Δsod1, and Δsod2 with K6001 background were employed and the anti-oxidative stress assay was performed. One new anti-aging lysophosphatidic acid (LPA) was obtained, and its structural and stereochemical characteristics were elucidated through spectroscopy and chemical derivatization. LPA can extend the replicative lifespan of K6001 at 10 and 30 µM (p < 0.001 and p < 0.01, respectively). This finding was comparable to the effect of resveratrol, a well-known anti-aging substance. However, the anti-aging activity of the compound on the four mutants was diminished. In the antioxidative stress assay, LPA improved the oxidative resistance of yeast cells. The new LPA may exert its anti-aging effect by improving the anti-oxidative ability of yeast cells. The genes of UTH1, SKN7, and SOD may also be involved in the action.
MeSH Terms
- Aging
- Arabidopsis
- DNA-Binding Proteins
- Heat-Shock Proteins
- Hydrogen Peroxide
- Lysophospholipids
- Membrane Proteins
- Mitochondrial Proteins
- Mutation
- Oxidative Stress
- Resveratrol
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins
- Stilbenes
- Superoxide Dismutase
- Superoxide Dismutase-1
- Transcription Factors
Keywords
- Anti-aging activity
- Arabidopsis thaliana
- K6001
- Skn7
- UTH1
- lysophosphatidic acid
We tested the hypothesis that exposure to a short-duration (1 h) increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, would attenuate age-induced impairments of vascular smooth muscle (VSM) constrictor responses in soleus muscle feed arteries (SFA) via the Rho pathway. SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized to 90 or 130 cmH2O for 1 h. Following the 1-h treatment, pressure in P130 arteries was lowered to 90 cmH2O for examination of vasoconstrictor responses to norepinephrine (NE), angiotensin II (Ang II), and phenylephrine (PE). To assess the role of the Rho pathway, vasoconstrictor responses were assessed in the absence or presence of a RhoA-kinase inhibitor (Y27632) or RhoA-kinase activator (LPA). Vasoconstrictor responses to NE, Ang II, and PE were impaired in old P90 SFA. Pretreatment of old SFA with increased pressure improved vasoconstrictor responses to NE, PE and Ang II. The beneficial effect of the pressure pretreatment in old SFA was eliminated in the presence of Y27632. In the presence of LPA, vasoconstrictor responses to Ang II were improved in old SFA such that responses were not different than young P90 SFA. These results indicate that a short-duration exposure to increased intraluminal pressure, to mimic pressure associated with a bout of exercise, attenuates or reverses the age-related decrement in VSM constrictor responses in SFA and that the beneficial response is mediated through Rho kinase.
MeSH Terms
- Aging
- Amides
- Angiotensin II
- Animals
- Arteries
- Endothelium, Vascular
- Male
- Muscle, Skeletal
- Muscle, Smooth, Vascular
- Norepinephrine
- Phenylephrine
- Physical Conditioning, Animal
- Pressure
- Pyridines
- Rats
- Rats, Inbred F344
- Vasoconstriction
- Vasoconstrictor Agents
- rho-Associated Kinases
Keywords
- Aging
- Fischer 344 rats
- Rho kinase
- Vasoconstriction
To determine the relationship between peripheral hearing loss (HL) in baby boomers (better-ear measure) and cognitive function, taking into account the impact of depression or cognitive reserve on this relationship and exploring binaural hearing. A prospective, epidemiology study. Data from 1,969 participants aged 45 to 66 years were collected in the Busselton Healthy Ageing Study. Participants were assessed using pure-tone air-conduction thresholds at octave frequencies (250; 500; 1,000; 2,000; 4,000; and 8,000 Hz). Hearing loss was grouped using 1) pure-tone averages across 4 frequencies (500 to 4000Hz) in the better ear (BE4FA) or 2) latent profile analysis (LPA) using all thresholds from both ears. Cognition was tested with the Cognitive Drug Research System, verbal fluency, and National Adult Reading Test (premorbid-IQ). Regression was used to determine the impact of HL relative to no HL on age and education-adjusted cognition, controlling for mood, sex, and premorbid-IQ. According to BE4FA, 4.7% had mild (26-40 dB) HL; 0.8% had moderate (41-60 dB) HL; and 0.3% had severe (61-80 dB) HL. Based on the LPA, 20.5% had high-frequency HL; 7.8% had mid- to high-frequency HL; and 1.9% had significant HL across all frequencies. The HL group was not a predictor of cognitive performance in any domain using BE4FA and explained just 0.5% and 0.4% of variance in continuity-of-attention and speed-of-memory retrieval using LPA. Critically, those with the worst hearing did not differ cognitively from those with the best. Hearing loss is not an important determinant of contemporaneous attention, memory, or executive function in middle-aged adults once age, education, depression, cognitive reserve, and sex are controlled. 4. Laryngoscope, 126:2367-2375, 2016.
MeSH Terms
- Aged
- Attention
- Audiometry, Pure-Tone
- Auditory Threshold
- Australia
- Cognition Disorders
- Cognitive Reserve
- Depression
- Female
- Hearing Loss
- Humans
- Male
- Memory
- Middle Aged
- Prospective Studies
- Regression Analysis
Keywords
- Hearing impairment
- aging
- cognition
- epidemiology
Autotaxin (ATX, Enpp2) is a secreted lysophospholipase D catalysing the production of lysophosphatidic acid, a pleiotropic growth factor-like lysophospholipid. Increased ATX expression has been detected in a number of chronic inflammatory diseases and different types of cancer, while genetic interventions have proven a role for ATX in disease pathogenesis. Therefore, ATX has emerged as a potential drug target and a large number of ATX inhibitors have been developed exhibiting promising therapeutic potential. However, the embryonic lethality of ATX null mice and the ubiquitous expression of ATX and LPA receptors in adult life question the suitability of ATX as a drug target. Here we show that inducible, ubiquitous genetic deletion of ATX in adult mice, as well as long-term potent pharmacologic inhibition, are well tolerated, alleviating potential toxicity concerns of ATX therapeutic targeting.
MeSH Terms
- Aging
- Animals
- Benzoxazoles
- Enzyme Activation
- Integrases
- Mice, Inbred C57BL
- Phosphoric Diester Hydrolases
- Piperazines
- Tamoxifen
This study seeks to examine the relationships between physical activity (PA), cognitive activity, and cognitive function for the purpose of developing future brain-fitness programs. A sample of 2,305 participants (age = 50-84, mean age: 63.1 years) was selected from the Midlife in the United States longitudinal study for analysis. The strength of the associations between the dependent variables (episodic memory and executive functions) and independent variables (three domains of PA and cognitive activity) were determined by hierarchical regression. Episodic memory regressed positively on leisure-time PA (LPA) and cognitive activity. Executive functions regressed positively on LPA and Cognitive activity, but negatively on job-related PA (JPA). The interaction effect (JPA × Cognitive activity) was nonsignificant. Community-dwelling participants are encouraged to engage in more LPA and cognitive activity to increase brain fitness. Further research may explore the distinctive effects of JPA.
MeSH Terms
- Aged
- Aged, 80 and over
- Cognitive Dysfunction
- Executive Function
- Female
- Humans
- Leisure Activities
- Life Style
- Male
- Memory, Episodic
- Middle Aged
- Motor Activity
Keywords
- aging
- cognitive activity
- episodic memory
- executive functions
- physical activity
This study aims to quantitatively assess the effects of vigorous and light physical activity (VPA, LPA) on static balance, gait and sit-to-stand (STS) tasks in a cohort of healthy older adults. To this end, 34 individuals of age >65 years were divided into two groups (n=17 each) who underwent 36 sessions (3×12 weeks) of PA characterized by different levels of intensity, assessed through continuous heart rate monitoring during the training session. Their balance and mobility were objectively evaluated on the basis of postural sway and time of STS measurements performed using a force platform. The main spatiotemporal parameters of gait (i.e. speed, stride and gait cycle duration, stance, swing and double support phase duration) were also acquired using a wearable inertial measurement unit. The results show that most gait parameters and STS time significantly improve in the VPA group but not in the LPA one. For the latter group a reduction only of swing phase duration was detected. PA also induced a generalized reduction of postural sway in both groups in the case of absence of visual input. These findings suggest that PA programs characterized by superior levels of intensity might be more suitable in generally improving static and dynamic daily motor tasks, while in terms of static balance acceptable results can be achieved even when only light activity is performed.
MeSH Terms
- Accidental Falls
- Aged
- Aged, 80 and over
- Aging
- Cohort Studies
- Exercise Test
- Gait
- Geriatric Assessment
- Heart Rate
- Humans
- Male
- Postural Balance
- Walking
Keywords
- Balance
- Elderly
- Gait
- Physical activity
- Postural sway
To evaluate in a sample of initially middle-aged municipal employees whether leisure time (LPA) or occupational physical activity (OPA) was associated with mobility limitation (ML) in old age. Prospective population-based follow-up. Municipalities in Finland. Public sector employees from the Finnish Longitudinal Study on Municipal Employees (FLAME) initially aged 44 to 58 (N = 5,200). Baseline data were collected in 1981, including LPA (average exercise within previous year: inactive (no exercise), moderate (some form of exercise ≤ 1 time per week), vigorous (brisk exercise ≥ 1 time per week)) and OPA (usual activities at work within previous year: light (light work sitting, standing, or moving around), moderate (moderate work moving around), vigorous (heavy physical work)). Number of MLs was assessed using a questionnaire (8 items) in 1985, 1992, 1997, and 2009; the latest mobility score available for each subject was used for analyses. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for LPA and OPA predicting ML were estimated in a joint Poisson regression model adjusted for survival data; the other type of PA; and sociodemographic, socioeconomic, and health-related factors. Mean age at baseline was 50.3 ± 3.6; 56.9% of participants were female. Participants with vigorous OPA in midlife had greater risk of a unit increase in ML in old age than those with light OPA (fully adjusted IRR = 1.09, 95% CI = 1.03-1.16). Participants with vigorous LPA had lower risk of ML than inactive participants (fully adjusted IRR = 0.81, 95% CI = 0.76-0.86). Findings suggest that LPA and OPA in midlife have independent, inverse effects on mobility in old age in terms of a harmful effect of vigorous OPA and a protective effect of vigorous LPA.
MeSH Terms
- Adult
- Female
- Finland
- Follow-Up Studies
- Forecasting
- Health Behavior
- Humans
- Leisure Activities
- Male
- Middle Aged
- Mobility Limitation
- Motor Activity
- Occupational Health
- Prospective Studies
- Risk Factors
- Surveys and Questionnaires
Keywords
- aging
- longitudinal studies
- mobility limitation
- occupational class
- physical activity