Showing papers in "Journals of Gerontology Series A-biological Sciences and Medical Sciences in 2018"

Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms.

Abstract: Consuming a Mediterranean diet rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases and increased life expectancy. Data from several randomized clinic trials have demonstrated a beneficial effect in the primary and secondary prevention of cardiovascular disease, type 2 diabetes, atrial fibrillation, and breast cancer. The exact mechanism by which an increased adherence to the traditional Mediterranean diet exerts its favorable effects is not known. However, accumulating evidence indicates that the five most important adaptations induced by the Mediterranean dietary pattern are: (a) lipid-lowering effect, (b) protection against oxidative stress, inflammation and platelet aggregation, (c) modification of hormones and growth factors involved in the pathogenesis of cancer, (d) inhibition of nutrient sensing pathways by specific amino acid restriction, and (e) gut microbiota-mediated production of metabolites influencing metabolic health. More studies are needed to understand how single modifications of nutrients typical of the Mediterranean diet interact with energy intake, energy expenditure, and the microbiome in modulating the key mechanisms that promote cellular, tissue, and organ health during aging.

Oral Frailty as a Risk Factor for Physical Frailty and Mortality in Community-Dwelling Elderly.

Abstract: Background Oral health is important for maintaining general health among the elderly. However, a longitudinal association between poor oral health and general health has not been reported. We investigated whether poor oral status can predict physical weakening (physical frailty, sarcopenia, and subsequent disability) and identified the longitudinal impact of the accumulated poor oral health (i.e. oral frailty) on adverse health outcomes, including mortality. Methods A total of 2,011 elderly individuals (aged ≥ 65 years) participated in the baseline survey of the Kashiwa study in 2012. At baseline, 16 oral status measures and covariates such as demographic characteristics were assessed. As outcomes, physical frailty and sarcopenia were assessed at baseline and at follow-up in 2013 and 2014. Physical independence and survival were assessed from 2012 to 2016 at the time of long-term care certification and time of death. Results Poor oral status as determined by the number of natural teeth, chewing ability, articulatory oral motor skill, tongue pressure, and subjective difficulties in eating and swallowing significantly predicted future physical weakening (new onsets of physical frailty, sarcopenia, and disability). Oral frailty was defined as co-existing poor status in ≥3 of the six measures. Sixteen per cent of participants had oral frailty at baseline, which was significantly associated with 2.4-, 2.2-, 2.3-, and 2.2-fold increased risk of physical frailty, sarcopenia, disability, and mortality, respectively. Conclusion Accumulated poor oral status strongly predicted the onset of adverse health outcomes, including mortality among the community-dwelling elderly. Prevention of oral frailty at an earlier stage is essential for healthy aging.

Evidence for the Domains Supporting the Construct of Intrinsic Capacity.

Abstract: Healthy ageing can be defined as "the process of developing and maintaining the functional ability that enables wellbeing in older age". Functional ability (i.e., the health-related attributes that enable people to be and to do what they have reason to value) is determined by intrinsic capacity (i.e., the composite of all the physical and mental capacities of an individual), the environment (i.e., all the factors in the extrinsic world that form the context of an individual's life), and the interactions between the two. This innovative model recently proposed by the World Health Organization has the potential to substantially modify the way in which clinical practice is currently conducted, shifting from disease-centered toward function-centered paradigms. By overcoming the multiple limitations affecting the construct of disease, this novel framework may allow the worldwide dissemination of a more proactive and function-based approach toward achieving optimal health status. In order to facilitate the translation of the current theoretical model into practice, it is important to identify the inner nature of its constituting constructs. In this article, we consider intrinsic capacity. Using the International Classification of Functioning, Disability and Health (ICF) framework as background and taking into account available evidence, five domains (i.e., locomotion, vitality, cognition, psychological, sensory) are identified as pivotal for capturing the individual's intrinsic capacity (and therefore also reserves) and, through this, pave the way for its objective measurement.

Measuring Frailty in Medicare Data: Development and Validation of a Claims-Based Frailty Index.

Abstract: Background Frailty is a key determinant of health status and outcomes of health care interventions in older adults that is not readily measured in Medicare data. This study aimed to develop and validate a claims-based frailty index (CFI). Methods We used data from Medicare Current Beneficiary Survey 2006 (development sample: n = 5,593) and 2011 (validation sample: n = 4,424). A CFI was developed using the 2006 claims data to approximate a survey-based frailty index (SFI) calculated from the 2006 survey data as a reference standard. We compared CFI to combined comorbidity index (CCI) in the ability to predict death, disability, recurrent falls, and health care utilization in 2007. As validation, we calculated a CFI using the 2011 claims data to predict these outcomes in 2012. Results The CFI was correlated with SFI (correlation coefficient: 0.60). In the development sample, CFI was similar to CCI in predicting mortality (C statistic: 0.77 vs. 0.78), but better than CCI for disability, mobility impairment, and recurrent falls (C statistic: 0.62-0.66 vs. 0.56-0.60). Although both indices similarly explained the variation in hospital days, CFI outperformed CCI in explaining the variation in skilled nursing facility days. Adding CFI to age, sex, and CCI improved prediction. In the validation sample, CFI and CCI performed similarly for mortality (C statistic: 0.71 vs. 0.72). Other results were comparable to those from the development sample. Conclusion A novel frailty index can measure the risk for adverse health outcomes that is not otherwise quantified using demographic characteristics and traditional comorbidity measures in Medicare data.

Associations of sarcopenia definitions, and their components, with the incidence of recurrent falling and fractures : The longitudinal aging study Amsterdam

Abstract: Background: The aim was to investigate the associations of sarcopenia as defined by European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) Sarcopenia Project, and their underlying components, with the incidence of recurrent falling and fractures. Methods: In 498 older men and women (mean age = 75.2 [SD = 6.4]) from the Longitudinal Aging Study Amsterdam (LASA), the sarcopenia components lean mass (DXA), handgrip strength (handheld dynamometer), and gait speed were measured. Data on falls (3-year follow-up) and fractures (10-year follow-up) were collected. Cox regression analyses were performed, adjusting for age, sex, and total body fat. Results: Recurrent falling occurred in 130 persons and 60 persons experienced a fracture during follow-up. Participants who were identified as sarcopenic based on the FNIH definitions had a more than 2-fold increased risk to become a recurrent faller. There was no association between sarcopenia based on the EWGSOP definition and incidence of recurrent falling. When the sarcopenia components were examined individually, only a low grip strength was associated with incidence of recurrent falling, independent of a low lean mass or a slow gait speed. Sarcopenia according to both definitions was not associated with incident fractures, which may be caused by low statistical power. Conclusion: Sarcopenia according to the FNIH definitions, but not according to the EWGSOP definition was associated with recurrent falling. When examining the individual components, only a low grip strength was independently associated with recurrent falling. No associations between sarcopenia with incidence of fractures were found.

Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival.

Abstract: Background Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly population, 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 more than 65 years (mean age 75.3 years, women 61.8%), without chronic liver disease, malignancies, or alcohol abuse. Frailty was defined according to Fried criteria, sarcopenia through peripheral Quantitative-Computed-Tomography (lowest gender-specific tertile of the residuals of a linear regression of muscle mass from height and fat mass), and disability as self-reported need for help in at least one basic daily living activity. Associations of ALT with overall and cardiovascular mortality were assessed by Cox-models with time-dependent covariates. Results ALT activity was inversely associated with frailty, sarcopenia, disability, and pyridoxine deficiency; however, higher ALT was confirmed to be protective with respect of overall and cardiovascular mortality even in multiple-adjusted models including all these covariates (overall: hazard ratio [HR] 0.98 [0.96-1], p = .02; cardiovascular: 0.94 [0.9-0.98], p < .01). The association between ALT activity and mortality was nonlinear (J-shaped), and subjects in the lower quintiles of ALT levels showed a sharply increased overall and cardiovascular mortality. Conclusions These results suggest that reduced ALT levels in older individuals can be considered as a marker of frailty, disability, and sarcopenia, and as an independent predictor of adverse outcomes. The possible relationship between reduced ALT and impaired hepatic metabolic functions should be explored.

Prevalence and Correlates of Frailty Among Community-Dwelling Chinese Older Adults: The China Health and Retirement Longitudinal Study.

Abstract: Background Frailty is an age-related clinical syndrome of decreased resilience to stressors and is associated with numerous adverse outcomes Although there is preponderance of literature on frailty in developed countries, limited investigations have been conducted in less developed regions including China—a country that has the world’s largest aging population We examined frailty prevalence in China by sociodemographics and geographic region, and investigated correlates of frailty

An international perspective on chronic multimorbidity: approaching the elephant in the room

Abstract: Multimorbidity is a common and burdensome condition that may affect quality of life, increase medical needs, and make people live more years of life with disability. Negative outcomes related to multimorbidity occur beyond what we would expect from the summed effect of single conditions, as chronic diseases interact with each other, mutually enhancing their negative effects, and eventually leading to new clinical phenotypes. Moreover, multimorbidity mirrors an accelerated global susceptibility and a loss of resilience, which are both hallmarks of aging. Due to the complexity of its assessment and definition, and the lack of clear evidence steering its management, multimorbidity represents one of the main current challenges for clinicians, researchers, and policymakers. The authors of this article recently reflected on these issues during two twin international symposia at the 2016 European Union Geriatric Medicine Society (EUGMS) meeting in Lisbon, Portugal, and the 2016 Gerontological Society of America (GSA) meeting in New Orleans, USA. The present work summarizes the most relevant aspects related to multimorbidity, with the ultimate goal to identify knowledge gaps and suggest future directions to approach this condition.

Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis.

Abstract: Biological aging measures have been proposed as proxies for extension of healthy life span in trials of geroprotective therapies that aim to slow aging. Several methods to measure biological aging show promise but it is not known if these methods are sensitive to changes caused by geroprotective therapy. We conducted analysis of two proposed methods to quantify biological aging using data from a recently concluded trial of an established geroprotector, caloric restriction. We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N = 220 nonobese adults to 25% caloric restriction (n = 145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n = 75) for 2 years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans.

Population Specific Biomarkers of Human Aging: A Big Data Study Using South Korean, Canadian, and Eastern European Patient Populations.

Abstract: Accurate and physiologically meaningful biomarkers for human aging are key to assessing antiaging therapies. Given ethnic differences in health, diet, lifestyle, behavior, environmental exposures, and even average rate of biological aging, it stands to reason that aging clocks trained on datasets obtained from specific ethnic populations are more likely to account for these potential confounding factors, resulting in an enhanced capacity to predict chronological age and quantify biological age. Here, we present a deep learning-based hematological aging clock modeled using the large combined dataset of Canadian, South Korean, and Eastern European population blood samples that show increased predictive accuracy in individual populations compared to population specific hematologic aging clocks. The performance of models was also evaluated on publicly available samples of the American population from the National Health and Nutrition Examination Survey (NHANES). In addition, we explored the association between age predicted by both population specific and combined hematological clocks and all-cause mortality. Overall, this study suggests (a) the population specificity of aging patterns and (b) hematologic clocks predicts all-cause mortality. The proposed models were added to the freely-available Aging.AI system expanding the range of tools for analysis of human aging.

Nutritional Supplementation With Physical Activity Improves Muscle Composition in Mobility-Limited Older Adults, The VIVE2 Study: A Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract: Background Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long-term nutritional supplementation in combination with physical activity in older adults remains unclear. Methods Mobility-limited (short physical performance battery [SPPB] ≤9) and vitamin D insufficient (serum 25(OH) D 9-24 ng/mL) older adults were recruited for this study. All subjects participated in a physical activity program. Subjects were randomized to consume a daily nutritional supplement (150 kcal, 20 g whey protein, 800 IU vitamin D, 119 mL beverage) or placebo (30 kcal, nonnutritive, 119 mL). In a prespecified secondary analysis, we examined total-body composition (dual energy X-ray absorptiometry), thigh composition (computed tomography), and muscle strength, power, and quality before and after the 6-month intervention. Results One hundred and forty-nine subjects were randomized into the study [mean (standard deviation, SD) age 78.5 (5.4) years; 46.3% female; mean (SD) short physical performance battery 7.9 (1.2); mean (SD) vitamin D 18.7 (6.4) ng/mL]. After the intervention period both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation lead to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018). Conclusions Six months of physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in further declines in intermuscular fat and improved muscle density compared to placebo. These results suggest nutritional supplementation provides additional benefits to mobility-limited older adults undergoing exercise training. ClinicalTrials.gov Identifier: NCT01542892.

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

Abstract: Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.

Cellular Senescence Biomarker p16INK4a+ Cell Burden in Thigh Adipose is Associated With Poor Physical Function in Older Women.

Abstract: Background Ample evidence implicates cellular senescence as a contributor to frailty and functional decline in rodents, but considerable effort remains to translate these findings to human aging. Methods We quantified senescence biomarker p16INK4a-expressing cells in thigh adipose tissue obtained from older women previously enrolled in a 5-month resistance training intervention, with or without caloric restriction (RT ± CR, n = 11 baseline, 8 pre-post-intervention pairs). Women in this subsample were older (72.9 ± 3.4 y) and overweight/obese (body mass index: 30.6 ± 2.4 kg/m2). p16INK4a+ cells were identified from 12 to 20 random visual fields/sample at 20× magnification (immunohistochemical, nuclear staining) and were present in all adipose samples. Results Cross-sectional associations were observed between p16INK4a+ cell burden and physical function, including grip strength (r = -0.74), 400-m walk time (r = 0.74), 4-m gait speed (r = -0.73), and self-perceived mobility (r = -0.78) (p ≤ .05). These relationships remained significant after independent adjustments for age and adiposity (p ≤ .05). p16INK4a+ cell abundance was lower following the intervention (pre: 5.47 ± 3.4%, post: 2.17 ± 1.1% count p16INK4a+ cells, p ≤ .05). Conclusions These results provide proof-of-concept that p16INK4a+ cells in thigh adipose are associated with physical function, and may be sensitive to change with RT ± CR in overweight/obese older women.

Death, Depression, Disability, and Dementia Associated With Self-reported Hearing Problems: A 25-Year Study.

Abstract: Background Hearing loss in older adults is suspected to play a role in social isolation, depression, disability, lower quality of life, and risk of dementia. Such suspected associations still need to be consolidated with additional research. With a particularly long follow-up, this study assessed the relationship between hearing status and four major adverse health events: death, dementia, depression, and disability. Methods Prospective community-based study of 3,777 participants aged ≥65 followed up for 25 years. At baseline, 1,289 reported hearing problems and 2,290 reported no trouble. The risk of occurrence of the negative outcomes, including death, dementia, depressive symptoms, disability in activities of daily living (ADL), and instrumental ADL (IADL), was assessed with Cox proportional hazards models. Results Adjusting for numerous confounders, an increased risk of disability and dementia was found for participants reporting hearing problems. An increased risk of depression was found in men reporting hearing problems. In additional exploratory analyses, such associations were not found in those participants using hearing aids. Mortality was not associated with self-reported hearing loss. Conclusions Our study confirms the strong link between hearing status and the risk of disability, dementia, and depression. These results highlight the importance of assessing the consequences of treating hearing loss in elders in further studies.

Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse

Abstract: Alzheimer's disease (AD) is rarely addressed in the context of aging even though there is an overlap in pathology We previously used a phenotypic screening platform based on old age-associated brain toxicities to identify the flavonol fisetin as a potential therapeutic for AD and other age-related neurodegenerative diseases Based on earlier results with fisetin in transgenic AD mice, we hypothesized that fisetin would be effective against brain aging and cognitive dysfunction in rapidly aging senescence-accelerated prone 8 (SAMP8) mice, a model for sporadic AD and dementia An integrative approach was used to correlate protein expression and metabolite levels in the brain with cognition It was found that fisetin reduced cognitive deficits in old SAMP8 mice while restoring multiple markers associated with impaired synaptic function, stress, and inflammation These results provide further evidence for the potential benefits of fisetin for the treatment of age-related neurodegenerative diseases

The Prevalence of Orthostatic Hypotension: A Systematic Review and Meta-Analysis.

Abstract: Background Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies. Methods MEDLINE, EMBASE, PubMed, Web of Science, and ProQuest were searched. Studies were included if participants were more than 60 years, were set within the community or within long-term care and diagnosis was based on a postural drop in systolic blood pressure (BP) ≥20 mmHg or diastolic BP ≥10 mmHg. Data were extracted independently by two reviewers. Random and quality effects models were used for pooled analysis. Results Of 23,090 identified records, 20 studies were included for community-dwelling older people (n = 24,967) and six were included for older people in long-term settings (n = 2,694). There was substantial variation in methods used to identify OH with differing supine rest duration, frequency and timing of standing BP, measurement device, use of standing and tilt-tables and interpretation of the diagnostic drop in BP. The pooled prevalence of OH in community-dwelling older people was 22.2% (95% CI = 17, 28) and 23.9% (95% CI = 18.2, 30.1) in long-term settings. There was significant heterogeneity in both pooled results (I2 > 90%). Conclusions OH is very common, affecting one in five community-dwelling older people and almost one in four older people in long-term care. There is great variability in methods used to identify OH.

The Contributions of Fiber Atrophy, Fiber Loss, In Situ Specific Force, and Voluntary Activation to Weakness in Sarcopenia.

Abstract: The contributions of fiber atrophy, fiber loss, in situ specific force, and voluntary activation to weakness in sarcopenia remain unclear. To investigate, 40 older (20 women; age 72 ± 4 years) and 31 younger adults (15 women, age 22 ± 3 years) completed measurements. The knee extensor maximal voluntary torque (MVC) was measured as well as voluntary activation, patella tendon moment arm length, muscle volume, and fascicle architecture to estimate in situ specific force. Fiber cross-sectional area (FCSA), fiber numbers, and connective tissue contents were also estimated from vastus lateralis biopsies. The MVC, quadriceps volume, and specific force were 39%, 28%, and 17% lower, respectively, in old compared with young, but voluntary activation was not different. The difference in muscle size was due in almost equal proportions to lower type II FCSA and fewer fibers. Five years later (n = 23) the MVC, muscle volume and voluntary activation in old decreased an additional 12%, 6%, and 4%, respectively, but there was no further change in specific force. In situ specific force declines relatively early in older age and reduced voluntary activation occurs later, but the overall weakness in sarcopenia is mainly related to loss of both type I and II fibers and type II fiber atrophy.

Failed Recovery of Glycemic Control and Myofibrillar Protein Synthesis With 2 wk of Physical Inactivity in Overweight, Prediabetic Older Adults.

Abstract: Background Physical inactivity impairs insulin sensitivity, which is exacerbated with aging. We examined the impact of 2 wk of acute inactivity and recovery on glycemic control, and integrated rates of muscle protein synthesis in older men and women. Methods Twenty-two overweight, prediabetic older adults (12 men, 10 women, 69 ± 4 y) undertook 7 d of habitual activity (baseline; BL), step reduction (SR; <1,000 steps.d-1 for 14 d), followed by 14 d of recovery (RC). An oral glucose tolerance test was used to assess glycemic control and deuterated water ingestion to measure integrated rates of muscle protein synthesis. Results Daily step count was reduced (all p < .05) from BL at SR (7362 ± 3294 to 991 ± 97) and returned to BL levels at RC (7117 ± 3819). Homeostasis model assessment-insulin resistance increased from BL to SR and Matsuda insulin sensitivity index decreased and did not return to BL in RC. Glucose and insulin area under the curve were elevated from BL to SR and did not recover in RC. Integrated muscle protein synthesis was reduced during SR and did not return to BL in RC. Conclusions Our findings demonstrate that 2 wk of SR leads to lowered rates of muscle protein synthesis and a worsening of glycemic control that unlike younger adults is not recovered during return to normal activity in overweight, prediabetic elderly humans. Clinical Trials Registration ClinicalTrials.gov identifier: NCT03039556.

High-Protein Foods and Physical Activity Protect Against Age-Related Muscle Loss and Functional Decline

Abstract: Background Some clinical trials suggest that protein supplementation enhances the effects of resistance exercise on skeletal muscle mass (SMM); fewer studies examine the effects of diets rich in protein-source foods on SMM and functional status among community-dwelling adults Methods Data from the Framingham Offspring study including diet (three-day records, exams 3 and 5), physical activity (exams 2 and 4), percent SMM (%SMM) (exams 6 and 7), and functional performance (exams 5 through 8) were used to evaluate independent and combined effects of physical activity and high-protein foods on adjusted mean %SMM (using analysis of covariance) and risk of functional decline (using Cox proportional hazard's models) Analyses were adjusted for such factors as age, education, height, smoking, and fruit and grain consumption) Results Higher intakes of protein-source foods (red meat, poultry, fish, dairy, and soy, nuts, seeds and legumes) were associated with higher %SMM over 9 years, particularly among women Men and women with higher intakes of foods from animal sources had a higher % SMM regardless of activity; beneficial effects of plant-based protein foods were only evident in physically active adults Active subjects with higher intakes of animal or plant protein-source foods had 35% lowest risks of functional decline Among less active individuals, only those consuming more animal protein-source foods had reduced risks of functional decline (HR: 07l; 95% CI: 050-101) Conclusion Higher intake of animal-protein foods, alone and especially in combination with a physically active lifestyle, was associated with preservation of muscle mass and functional performance in older adults

The Prevalence of Vitamin D Deficiency and the Determinants of 25(OH)D Concentration in Older Irish Adults: Data From The Irish Longitudinal Study on Ageing (TILDA).

Abstract: Background Few data are available examining the determinants of vitamin D status exclusively in older adults. We aimed to investigate the prevalence and determinants of vitamin D deficiency in a representative sample of the older Irish population (aged 50-98 years). Methods The concentration of 25-hydroxyvitamin D (25(OH)D) was measured in 5,356 community-dwelling older Irish adults from The Irish Longitudinal Study on Ageing (TILDA). Detailed demographic, geographic, lifestyle, and socioeconomic factors were assessed by questionnaire. Proportions of deficiency prevalence were generated by season sampled. Linear regression was used to investigate the association between 25(OH)D concentration and reported risk factors. Results The prevalence of deficiency (25(OH)D 80 years). The main predictors (p < .05) of 25(OH)D concentration were supplement use (coefficient nmol/L: 27.2 [95% CI: 15.3-39.2]), smoking (-8.9 [-12.6--5.2]), summer season (5.9 [2.7-9.1]), and obesity (-4.0 [-6.3--1.7]). Conclusion Vitamin D deficiency is common among older Irish adults. These data indicate the need for targeted strategies within sections of the older population to improve vitamin D status.

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

Abstract: Background Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Methods Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Results Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Conclusions Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia.

Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.

Abstract: Background Sarcopenia affects more than 10% of older adults. Next to age-associated physiologic changes, diseases like diabetes or inflammatory, neurological, malignant and endocrine disorders may contribute to the development of sarcopenia. Likewise, polypharmacy, i.e., multiple drug use, is common among older adults. Although the two conditions frequently co-occur, the association of polypharmacy with sarcopenia has not yet been examined. We investigated the association of polypharmacy and sarcopenia in a large cohort of community-dwelling older adults (60-84 years). Methods Thousand five hundred and two participants from the Berlin Aging Study II were included. Polypharmacy was defined as concurrent use of 5 or more drugs (prescription and nonprescription). Body composition was assessed with dual-energy X-ray absorptiometry, and appendicular lean mass (ALM) was calculated as sum of the four limbs' lean mass. Sarcopenia was defined as low ALM-to-body mass index (BMI)-ratio using validated sex-specific cutoffs. Results Mean age was 68.7 ± 3.7 years, 50.7% were female. The median (interquartile range) number of drugs was 2 (1-4); 21.1% of subjects reported regular use of ≥5 drugs. Subjects with polypharmacy were more often sarcopenic according to the applied ALM/BMI-cutoffs (16.3% vs 6.9%, p < 0.001), with a higher BMI (p < 0.001) and lower ALM/BMI (p < 0.001), but no significant difference in mean ALM. Notably, polypharmacy was also associated with higher rates of reduced gait speed and exhaustion. Even after multivariable adjustment (sex, age, comorbid conditions and physical activity) polypharmacy was consistently associated with a significantly increased likelihood of sarcopenia (odds ratio = 2.24, 95% confidence interval [CI] = 1.33-3.75). Conclusion Polypharmacy is associated with clinically relevant sarcopenia, as assessed by a low ALM/BMI.

Body Mass Index and Decline in Cognitive Function in Older Black and White Persons

Abstract: Background While body mass index (BMI) is higher in black compared to white persons, little is known about BMI and change in cognition in cohorts with a large proportion of blacks. We examine relations of BMI with decline in global cognition and five cognitive domains, in older blacks and whites, and determine whether relations differ by race. Methods Participants were 2,134 persons without baseline dementia (33% black; 75% women; mean age =77.9 [range 53-100] and education = 14.7 years, Mini-Mental State Examination = 28.0), enrolled in one of two longitudinal, community-based cohort studies of aging (Minority Aging Research Study; Rush Memory and Aging Project). Summary scores of global cognition and five domains were based on 19 neuropsychological tests administered annually. Mixed-effects models, controlling for age, sex, education, and race, were used to examine the relation of baseline BMI to change in cognition. Results Baseline BMI = 28.4 units (30.3 in blacks [95% confidence interval (CI): 27.2-27.7]; 27.4 in whites [95% CI: 29.8-30.7]). During a mean annual follow-up of 6 years (SD = 4), lower baseline BMI was related to faster decline in global cognition (p = .002), and semantic memory (p .08). The relationship of BMI with change in cognition was not modified by race (all p > .09). Conclusions Late-life lower BMI relates to faster rates of decline in cognition, specifically semantic memory and episodic memory, in both blacks and whites. The effect of BMI on cognition appears to be similar in both racial groups.

Sex Differences in Aging: Genomic Instability.

Abstract: Aging is characterized by decreasing physiological integration, reduced function, loss of resilience, and increased risk of death Paradoxically, although women live longer, they suffer greater morbidity particularly late in life These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist While these differences are ubiquitous in humans, evidence of sex differences in longevity and health for other species is more equivocal Among fruit flies, nematodes, and mice, sex differences in lifespan vary depending on strain and treatment In this review, we focus on sex differences in age-related alterations in DNA damage and mutation rates, telomere attrition, epigenetics, and nuclear architecture We find that robust sex differences exist, eg, the higher incidence of DNA damage in men compared to women, but sex differences are not often conserved between species For most mechanisms reviewed here, there are insufficient data to make a clear determination regarding the impact of sex, largely because sex differences have not been analyzed Overall, our findings reveal an urgent need for well-designed studies that explicitly examine sex differences in molecular drivers of aging

Adherence and Persistence Among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis.

Abstract: Background: Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. Methods: As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analysed via descriptive methods and meta-analysis using random-effect modeling. Results: Data from > 3 million older statin users in 82 studies conducted in over 40 countries were analysed. At 1-year follow up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged > 75 than those aged 65-75 years. At 3 and ≥ 10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were non-adherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. Conclusions: There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realised.

High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice.

Abstract: 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. Baseline and end point assessments included body composition, physical performance, and frailty based on criteria from the Fried physical frailty scale. HIIT-trained mice demonstrated dramatic improvement in grip strength (HIIT 10.9% vs -3.9% in sedentary mice), treadmill endurance (32.6% vs -2.0%), and gait speed (107.0% vs 39.0%). Muscles from HIIT mice also exhibited greater mass, larger fiber size, and an increase in mitochondrial biomass. Furthermore, HIIT exercise led to a dramatic reduction in frailty scores in five of six mice that were frail or prefrail at baseline, with four ultimately becoming nonfrail. The uphill treadmill HIIT exercise sessions were well tolerated by aged mice and led to performance gains, improvement in underlying muscle physiology, and reduction in frailty.

Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity

Abstract: Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals. Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions. Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin. Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults.

Exercise Training for Preventing Dementia, Mild Cognitive Impairment, and Clinically Meaningful Cognitive Decline: A Systematic Review and Meta-analysis.

Abstract: Background To assess the effects of long-term exercise on the onset of dementia, mild cognitive impairment (MCI), and other clinically meaningful cognitive decline in the elderly adults. Methods Systematic review with preplanned meta-analysis. Electronic searches were performed between November 2016 and May 2017. Randomized controlled trials (RCTs) examining the effects of long-term exercise (intervention length 12 months or longer) on the onset of dementia, MCI, or clinically meaningful cognitive decline in older adults without dementia at baseline were eligible. Two authors extracted the data independently. Four binary outcomes were defined: dementia onset, MCI onset, other clinically meaningful cognitive decline, and any of these three outcomes combined. Results Five studies (n = 2,878 participants randomized) were included in this review. Outcomes' incidence for exercisers and controls were, respectively: 3.7% (n = 949) and 6.1% (n = 1,017) for dementia (three studies), 10.2% (n = 686) and 9.1% (n = 682) for MCI (one study), 14.5% (n = 124) and 15.4% (n = 123) for other clinically meaningful cognitive decline (two studies), and 11.4% (n = 1,073) and 12.5% (n = 1,140) for all outcomes combined. Meta-analyses found no significant effects of exercise for reducing the risk of dementia, MCI, other clinically meaningful cognitive decline, or all outcomes combined. Conclusions Evidence from RCTs is limited and does not support that exercise reduces the risk of developing clinically important cognitive outcomes. Further long-term exercise RCTs are needed before solid conclusions can be drawn.

Effects of a Primary Care-Based Multifactorial Intervention on Physical and Cognitive Function in Frail, Elderly Individuals: A Randomized Controlled Trial.

Abstract: Background Detecting and managing frailty at early stages can prevent disability and other adverse outcomes. The study aim was to evaluate whether a multifactorial intervention program could modify physical and cognitive frailty parameters in elderly individuals. Methods We conducted a multicenter, randomized, single-blind, parallel-group trial in community-living prefrail/frail elderly individuals in Barcelona. A total of 352 patients, aged ≥65 years old with positive frailty screening, was randomized into two groups to receive a 12-week multidisciplinary intervention or usual care, with concealed allocation. The intervention consisted of: exercise training, intake of hyperproteic nutritional shakes, memory training, and medication review. Main outcome assessments with multivariate analysis were conducted at 3 and 18 months. Results A total of 347 participants (98.6%) completed the study, mean age 77.3 years, 89 prefrail subjects (25.3%), and 75.3% female (n = 265). Eighteen-month assessments were performed in 76% of the sample. After 3 and 18 months, adjusted means difference between-groups showed significant improvements for the intervention group in all comparisons: Short Physical Performance Battery score improved 1.58 and 1.36 points (p < .001), handgrip strength 2.84 and 2.49 kg (p < .001), functional reach 4.3 and 4.52 cm (p < .001), and number of prescriptions decreased 1.39 and 1.09 (p < .001), respectively. Neurocognitive battery also showed significant improvements across all dimensions at 3 and 18 months. Conclusions A physical, nutritional, neurocognitive, and pharmacological multifaceted intervention was effective in reversing frailty measures both at short-term and 18 months. Lasting benefits of a multi-intervention program among frail elderly individuals encourage its prioritization.

Measures of Biologic Age in a Community Sample Predict Mortality and Age-Related Disease: The Framingham Offspring Study

Abstract: Background We tested the association of biologic age (BA) measures constructed from different types of biomarkers with mortality and disease in a community-based sample. Methods In Framingham Offspring participants at Exams 7 (1998-2001, mean age 62 ± 10) and 8 (2005-2008, mean age 67 ± 9), we used the Klemera-Doubal method to estimate clinical BA and inflammatory BA and computed the difference (∆age) between BA and CA. Clinical ∆age was computed at Exam 2 (1979-1983, mean age 45 ± 10). At Exam 8, we computed measures of intrinsic and extrinsic epigenetic age. Participants were followed through 2014 for outcomes. Cox proportional hazards models tested the association of each BA estimate with each outcome adjusting for covariates. Results Sample sizes ranged from 2532 to 3417 participants. In multivariable models, each 1-year increase in clinical ∆age at Exam 2 (hazard ratio [HR] = 1.04-1.06, p < 2 × 10-16) and clinical ∆age and inflammatory ∆age at Exam 7 significantly increased the hazards of mortality and incident cardiovascular disease (HR = 1.01-1.05, p < 2 × 10-7), whereas inflammatory ∆age increased the hazards of cancer (HR = 1.01, p < .05). At Exam 8, increased clinical ∆age, inflammatory ∆age, and extrinsic epigenetic age all significantly increased the hazard of mortality (HR = 1.03-1.05, all p < .05); clinical ∆age and inflammatory ∆age increased cardiovascular disease risk (HR = 1.04-1.05, all p < .01); and clinical ∆age increased cancer risk (HR = 1.03, p < .01) when all three BA measures were included in the model. Intrinsic epigenetic age was not significantly associated with any outcome. Conclusions Our findings suggest BA measures may be complementary in predicting risk for mortality and age-related disease.