Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

The greatest risk factor for Alzheimer's disease (AD) is advanced age, but the reason for this association remains unclear. Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by clathrin-mediated or clathrin-independent endocytosis. Changes in endocytosis in AD have been identified. We hypothesised that endocytic protein expression is altered during ageing, thus influencing the likelihood of developing AD by increasing Aβ production. We explored how levels of endocytic proteins, APP, its metabolites, secretase enzymes and tau varied with age in cortical brain samples from men of three age ranges (young (20-30), middle-aged (45-55) and old (70-90)) with no symptoms of dementia...

Acarbose, an alpha-glucosidase inhibitor used in treating type 2 diabetes, impairs complex carbohydrate digestion and absorption and extends lifespan in mice (without a requisite reduction in food intake). To assess sex-differential effects coincident with calorie restriction versus a non-restricted longevity enhancing intervention, we evaluated the metabolite profiles (by LC/MS) from livers and cecal contents of C57BL/6J mice (n=4/sex/group,) which were maintained for 10 months under one of three diet treatments: ad libitum control diet (CON), ad libitum control diet containing 0...

Background: This study examines effects of mobility and multimorbidity on hospitalization and inpatient and post-acute care (PAC) facility days among older men. Methods: Prospective study of 1701 men (mean age 79.3 years) participating in MrOS Study Year 7 (Y7) examination (2007-2008) linked with their Medicare claims. At Y7, mobility ascertained by usual gait speed and categorized as poor, intermediate, or good. Multimorbidity quantified by applying Elixhauser algorithm to inpatient and outpatient claims and categorized as none, mild-moderate, or high...

In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome...

The escalating increase in retirees living beyond their 8th decade brings increased prevalence of aging-related impairments, including locomotor impairment (Parkinsonism) which may affect ~50% of those reaching age 80, but has no confirmed neurobiological mechanism. Lifestyle strategies that attenuate motor decline, and its allied mechanisms, must be identified. Aging studies report little to moderate loss of striatal dopamine (DA) or tyrosine hydroxylase (TH) in nigrostriatal terminals, in contrast to ~70-80% loss associated with bradykinesia onset in Parkinson's disease...

Background: Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly, the determinants subtending this association have been poorly explored. To gain insight into this topic, we analyzed data from a prospective population-based database (InCHIANTI study) in which frailty, disability, sarcopenia and pyridoxine levels were systematically assessed. Methods: Data are from 765 participants aged >65 years (mean age 75...

Background: This study sought to determine the association between levels of physical activity and mobility difficulties and time to death while accounting for the effect of several confounders. We also examined the possible interaction between them and how various daily-life mobility difficulties could predict all-cause mortality. Methods: A nationally-representative sample of 2,074 non-institutionalized adults aged 60 years and older was analyzed. Vital status over a 3-year follow-up period was ascertained through national registers or by asking participants' relatives...

Sarcopenia and frailty are highly prevalent in older individuals, increasing the risk of disability and loss of independence. High intensity interval training (HIIT) may provide a robust intervention for both sarcopenia and frailty by achieving both strength and endurance benefits with lower time commitments than other exercise regimens. To better understand the impacts of HIIT during aging, we compared 24-month-old C57BL/6J sedentary mice with those that were administered 10-minute uphill treadmill HIIT sessions three times per week over 16 weeks...

Background: Inadequate sleep is correlated with morbidity and mortality among older adults. However, the longitudinal relationship between subjective sleep quality and risk of falls in the elderly remains to be clarified. Methods: Study participants were from Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) sites (1071 community-dwelling people ≧65 years of age, mean, 71 years). Subjective sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI)...

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No abstract text is available yet for this article.

Background: Diabetes has been linked to dementia risk; however, the cognitive trajectories in older adults with diabetes remain unclear. We aimed to investigate the effect of prediabetes and diabetes on cognitive trajectories among cognitively intact older adults in a long-term follow-up study. Methods: Within the Swedish Adoption/Twin Study of Aging, 793 cognitively intact older adults aged ≥50 were identified at baseline and followed for up to 23 years. Based on standardized scores from 11 cognitive tests, administered at baseline and up to seven follow-ups, four cognitive domains (verbal abilities, spatial/fluid, memory, perceptual speed) were identified by principal-component analysis...

Background: US seniors' digital health and everyday technology use when their health declines are unknown. Methods: Longitudinal cohort using the National Health and Aging Trends Study, a nationally-representative, annually-administered sample of community-dwelling Medicare beneficiaries (n=4037). We used difference-in-differences to assess the adjusted difference (AD) in technology use from 2011-2014 between those with and without health declines. Health decline measures included new-onset dementia; new-onset depression; decreases in activities of daily living (ADLs), short physical performance battery (SPPB), grip strength, and self-reported health; relocation to nursing facility; increased hospitalizations; and new-onset comorbidity...

Background: Multimorbidity is an important health outcome but is difficult to quantify. We recently developed a multimorbidity-weighted index (MWI) and herein assess its performance in an independent nationally-representative cohort. Methods: Health and Retirement Study (HRS) participants completed an interview on physician-diagnosed chronic conditions and physical functioning. We determined the relationship of chronic conditions on physical functioning and validated these weights with the original, independently-derived MWI...

Background: Although falls in older adults are related to multiple risk factors, these factors have commonly been studied individually. We aimed to identify risk profiles for injurious falls in older adults by detecting clusters of established risk factors and quantifying their impact on fall risk. Methods: Participants were 2566 people, aged ≥60 years, from the population-based Swedish National Study on Aging and Care in Kungsholmen. Injurious falls was defined as hospitalization for or receipt of outpatient care because a fall...

No abstract text is available yet for this article.

Background: With the continued rise in the proportion of the oldest-old in high income countries, it is of interest to know whether the functional health of today's oldest-olds is better or worse than in previous cohorts. Using two Danish centenarian birth cohorts born twenty years apart we aimed at investigating if the later born cohort had better functioning in terms of activities of daily living (ADL). Methods: Identification, methodology and assessment instruments were identical in the 1895-West and 1915-West Birth Cohort Studies: All persons living in the western part of Denmark and turning 100 years old in 1995 and 2015, respectively...

Background.: Hospitalization is a major risk factor for functional decline, disability, loss of independence, and mortality in older adults. Evidence-based interventions to improve functional recovery from hospitalization are difficult to evaluate and implement in geriatric patients. The goal of this pilot study was to test the feasibility of recruiting geriatric inpatients and implementing pragmatic interventions to improve physical function following hospitalization. Methods...

BACKGROUND.: We examined associations of three markers of subclinical cardiovascular disease (CVD) (intimal-medial thickening (IMT); coronary artery calcification (CAC); and ankle-brachial index (ABI)) with changes in self-reported walking over time. METHODS.: Data were from 6,490 MESA participants (aged 45-84 years), free of clinical CVD at baseline. Outcomes, assessed four times over 11 years, included self-reported walking pace (none to striding pace; score, 0-4), and total walking time (minutes/week)...

Age-related changes in primary lymphoid organs are well described. Less is known about age-related changes affecting peripheral lymphoid organs, although defects in old peripheral lymph nodes (pLN) were recently described in both steady state and during viral infection. To address whether such pLN defects were intrinsic to old T cells or extrinsic (due to aging microenvironment) we employed heterochronic parabiosis. We found no age-related intrinsic or extrinsic barriers to T cell circulation and seeding of pLN, spleen and bone marrow...