Showing papers in "Journals of Gerontology Series A-biological Sciences and Medical Sciences in 2011"

Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice

Abstract: Rapamycin was administered in food to genetically heterogeneous mice from the age of 9 months and produced significant increases in life span, including maximum life span, at each of three test sites. Median survival was extended by an average of 10% in males and 18% in females. Rapamycin attenuated age-associated decline in spontaneous activity in males but not in females. Causes of death were similar in control and rapamycin-treated mice. Resveratrol (at 300 and 1200 ppm food) and simvastatin (12 and 120 ppm) did not have significant effects on survival in male or female mice. Further evaluation of rapamycin's effects on mice is likely to help delineate the role of the mammalian target of rapamycin complexes in the regulation of aging rate and age-dependent diseases and may help to guide a search for drugs that retard some or all of the diseases of aging.

Hearing Loss Prevalence and Risk Factors Among Older Adults in the United States

Abstract: Background. Hearing loss has been associated with cognitive and functional decline in older adults and may be amenable to rehabilitative interventions, but national estimates of hearing loss prevalence and hearing aid use in older adults are unavailable. Methods. We analyzed data from the 2005–2006 cycle of the National Health and Nutritional Examination Survey, which is the first cycle to ever incorporate hearing assessment in adults aged 70 years and older. Audiometry was performed in 717 older adults, and data on hearing aid use, noise exposure, medical history, and demographics were obtained from interviews. Analyses incorporated sampling weights to account for the complex sampling design and yield results that are generalizable to the U.S. population. Results. The prevalence of hearing loss defined as a speech frequency pure tone average of more than 25 dB in the better ear was 63.1% (95% confidence interval: 57.4–68.8). Age, sex, and race were the factors most strongly associated with hearing loss after multivariate adjustment, with black race being substantially protective against hearing loss (odds ratio 0.32 compared with white participants [95% confidence interval : 0.19–0.53]). Hearing aids were used in 40.0% (95% confidence interval: 35.1 –44.8) of adults with moderate hearing loss, but in only 3.4% (95% confidence interval : 0.8–6.0) of those with a mild hearing loss. Conclusion. Hearing loss is prevalent in nearly two thirds of adults aged 70 years and older in the U.S. population. Additional research is needed to determine the epidemiological and physiological basis for the protective effect of black race against hearing loss and to determine the role of hearing aids in those with a mild hearing loss.

The Measurement of Multiple Chronic Diseases—A Systematic Review on Existing Multimorbidity Indices

Abstract: Multimorbidity, defined as the coexistence of 2 or more chronic diseases, is a common phenomenon especially in older people. Numerous efforts to establish a standardized instrument to assess the level of multimorbidity have failed until now, and indices are primarily characterized by their high heterogeneity. Thus, the objective is to provide a comprehensive overview on existing instruments on the basis of a systematic literature review.

Hearing Loss and Cognition Among Older Adults in the United States

Abstract: sample of older adults. Methods. We analyzed data from the 1999 to 2002 cycles of the National Health and Nutritional Examination Survey during which participants aged 60–69 years (n = 605) underwent both audiometric and cognitive testing. Hearing loss was defined by a pure tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better hearing ear. Cognitive testing consisted of the Digit Symbol Substitution Test (DSST), a nonverbal test that assesses executive function and psychomotor processing. Data on hearing aid use, demographics, and medical history were obtained from interviews. Regression models were used to examine the association between hearing loss and cognition while adjusting for confounders. Analyses incorporated sampling weights to yield results that are generalizable to the U.S. population. Results. Greater hearing loss was significantly associated with lower scores on the DSST after adjustment for demo graphic factors and medical history (DSST score difference of −1.5 [95% confidence interval : −2.9 to −0.23] per 10 dB of hearing loss). Hearing aid use was positively associated with cognitive functioning (DSST score difference of 7.4 [95% confidence interval : −0.62 to 15.4]). The reduction in cognitive performance associated with a 25 dB hearing loss was equivalent to the reduction associated with an age difference of 7 years. Conclusions. Hearing loss is independently associated with lower scores on the DSST. Further research is needed to determine whether hearing loss is a modifiable risk factor or an early marker of cognitive decline.

Predictive Value of the Short Physical Performance Battery Following Hospitalization in Older Patients

Abstract: HOSPITALIZATION for an acute medical event represents a stressful and potentially hazardous event for older persons. After discharge from the hospital, older patients often experience negative short- and long-term consequences, including functional decline, disability, rehospitalization, nursing home admission, and mortality (1–4). For example, the Hospital Outcomes Projects for the Elderly estimated that in a sample of acutely ill medical patients, as many as 19% had activity of daily living (ADL) decline and 40% had instrumental activity of daily living (IADL) decline in the 3 months after hospital discharge compared with their disability status prior to the index hospitalization (5). Identification of patients at high risk of functional decline or other adverse events after hospital discharge is of paramount importance for posthospital discharge assessment and management and for the prevention of these common negative outcomes. Very old frail patients and those with preadmission functional limitation are at higher risk of posthospital complications; nevertheless, the ability of medical diagnoses and traditional clinical assessment to discriminate high- and low-risk groups is limited (6). Objective measures of physical performance may prove an additional and useful clinical tool for risk stratification. Despite a large body of evidence demonstrating the predictive value of different mobility performance tests in terms of various adverse outcomes (7–11), the use of physical performance measures in the acute care clinical setting has received little attention so far (12). The Short Physical Performance Battery (SPPB), a set of objective measures of lower extremity physical performance, was highly predictive of subsequent disability, hospitalization, institutionalization, and mortality in community-dwelling elders in epidemiological studies and outpatient clinics (13,14). Recently, we have demonstrated that the SPPB can be feasibly and safely used to evaluate the functional status of acutely ill geriatric patients admitted to the hospital for serious medical conditions and that the SPPB score can provide important short-term prognostic information (15). What has not been evaluated is whether this simple battery of performance tests can capture change in function in the immediate period posthospitalization and predict long-term outcomes after hospital discharge. The aim of the present project was to determine whether SPPB score assessed at hospital discharge and sequential SPPB assessment in the first month after discharge are predictive of subsequent functional decline and risk of rehospitalization and mortality over a 12-month follow-up. We hypothesized that, even after adjusting for the presence of multiple medical conditions, patients with poorer SPPB score at discharge and those with immediate decline in SPPB score after discharge would be at greater risk of ADL decline, rehospitalization, and death.

Is Telomere Length a Biomarker of Aging? A Review

Abstract: Telomeres, the DNA-protein structures located at the ends of chromosomes, have been proposed to act as a biomarker of aging. In this review, the human evidence that telomere length is a biomarker of aging is evaluated. Although telomere length is implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal. More studies examining the relationships between telomere length and mortality and with measures that decline with "normal" aging in community samples are required. These studies would benefit from longitudinal measures of both telomere length and aging-related parameters.

fNIRS Study of Walking and Walking While Talking in Young and Old Individuals

Abstract: Background. Evidence suggests that gait is influenced by higher order cognitive and cortical control mechanisms. However, less is known about the functional correlates of cortical control of gait. Methods. Using functional near-infrared spectroscopy, the current study was designed to evaluate whether increased activations in the prefrontal cortex (PFC) were detected in walking while talking (WWT) compared with normal pace walking (NW) in 11 young and 11 old participants. Specifically, the following two hypotheses were evaluated: (a ) Activation in the PFC would be increased in WWT compared with NW. (b) The increase in activation in the PFC during WWT as compared with NW would be greater in young than in old participants. Results. Separate linear mixed effects models with age as the two-level between-subject factor, walking condition (NW vs WWT) as the two-level repeated within-subject factor, and HbO2 levels in each of the 16 functional near-infrared spectroscopy channels as the dependent measure revealed significant task effects in 14 channels, indicating a robust bi lateral increased activation in the PFC in WWT compared with NW. Furthermore, the group-by-task interaction was significant in 11 channels with young participants showing greater WWT-related increase in HbO2 levels compared with the old participants.

Virtual Reality for Gait Training: Can It Induce Motor Learning to Enhance Complex Walking and Reduce Fall Risk in Patients With Parkinson's Disease?

Abstract: Background Gait and cognitive disturbances are common in Parkinson's disease (PD). These deficits exacerbate fall risk and difficulties with mobility, especially during complex or dual-task walking. Traditional gait training generally fails to fully address these complex gait activities. Virtual reality (VR) incorporates principles of motor learning while delivering engaging and challenging training in complex environments. We hypothesized that VR may be applied to address the multifaceted deficits associated with fall risk in PD. Methods Twenty patients received 18 sessions (3 per week) of progressive intensive treadmill training with virtual obstacles (TT + VR). Outcome measures included gait under usual-walking and dual-task conditions and while negotiating physical obstacles. Cognitive function and functional performance were also assessed. Results Patients were 67.1 ± 6.5 years and had a mean disease duration of 9.8 ± 5.6 years. Posttraining, gait speed significantly improved during usual walking, during dual task, and while negotiating overground obstacles. Dual-task gait variability decreased (ie, improved) and Trail Making Test times (parts A and B) improved. Gains in functional performance measures and retention effects, 1 month later, were also observed. Conclusions To our knowledge, this is the first time that TT + VR has been used for gait training in PD. The results indicate that TT + VR is viable in PD and may significantly improve physical performance, gait during complex challenging conditions, and even certain aspects of cognitive function. These findings have important implications for understanding motor learning in the presence of PD and for treating fall risk in PD, aging, and others who share a heightened risk of falls.

Leukocyte Telomere Length and Mortality in the Cardiovascular Health Study

Abstract: TELOMERE shortening has been intrinsically linked to cell division and is a key determinant of replicative senescence of cultured somatic cells (1,2). Leukocyte telomere length (LTL) and its age-dependent shortening, that is LTL dynamics, have been the focus of intense investigations. LTL has been reported to be associated with age (3,4), gender (5,6), and many age-related diseases (7–14) as well as measures of general health (15,16). Several studies have evaluated associations between LTL and mortality with conflicting results; some observing that LTL was inversely related to mortality (17,18,20–24), whereas others have not (16,19,25,26). In addition, the mechanistic connection between LTL and mortality is an enigma and a number of problems have been cited in epidemiological studies (27,28). The question remains whether LTL is an index of aging and longevity or if its dynamics, which may mirror the kinetics of the hematopoietic stem cells (29), are actively engaged in determining end-of-life or age-related pathology (27,30). The Cardiovascular Health Study (CHS) provides the opportunity to evaluate the association between survival and LTL using a large cohort of adults aged 65 years and older (31). In addition to providing a large sample size, the CHS has been well characterized in terms of health status and incident cardiovascular disease. All participants have been followed to ascertain death and classified by trained clinicians for specific cause of death (32). Over the last several years, LTL was measured in a subset of CHS participants. In this article, we have utilized mortality and other data collected in the CHS to answer the following questions: (a) Is LTL associated with total mortality in adults aged 65 years and older? (b) Do associations between LTL and mortality differ by cause of death? (c) Are associations modified by factors including age, sex, race, or other variables?

Clinical Meaningfulness of the Changes in Muscle Performance and Physical Function Associated With Testosterone Administration in Older Men With Mobility Limitation

Abstract: MOBILITY limitation, a common geriatric condition, affects an individual’s quality of life, health care costs, and resource utilization while being predictive of disability, risk of hospitalization, and mortality (1–5). Among the function promoting therapies that are being developed for the treatment of functional limitations, androgens are the farthest in development. Testosterone levels are associated with skeletal muscle mass, lower extremity strength, and physical function (6–12). Men with low free testosterone are at increased risk of mobility limitation and its progression (8). Testosterone supplementation increases skeletal muscle mass (13–21), but its effects on muscle strength and physical function have been inconsistent across trials (13–21). Most testosterone trials have been conducted in healthy older men without functional limitations; the safety and efficacy of testosterone in improving muscle performance and physical function have not been demonstrated in older individuals with mobility limitation. The Testosterone in Older Men with Mobility Limitations (TOM) Trial was a placebo-controlled randomized trial (22,23), whose aim was to determine whether testosterone therapy in older men with mobility limitation and low total or free testosterone levels improves lower extremity muscle strength and physical function (22). As reported recently (23), because of a significantly higher incidence of adverse cardiovascular events in men assigned to the testosterone arm, the trial’s Data and Safety Monitoring Board recommended that further enrollment and administration of study medications to participants be discontinued. Here, we evaluated the clinical meaningfulness of the effects of intervention on performance-based as well as self-reported measures of muscle performance and physical function in relation to participant’s perception of change. To determine whether changes in the measures of muscle performance, skeletal muscle mass, and physical function were patient important and thus clinically meaningful, we categorized the participants as “improved” or “not improved” based on whether the change in outcome exceeded the minimally important difference (MID), determined using an anchor-based method within this trial. We analyzed the factors associated with improvements in outcomes and explored the relation between change in efficacy outcomes and adverse events.

The Lifestyle Interventions and Independence for Elders Study: Design and Methods

Abstract: Background. As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking. A Phase 3 randomized controlled trial is needed to fill this evidence gap. Methods. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled trial designed to compare a supervised moderate-intensity physical activity program with a successful aging health education program in 1,600 sedentary older persons followed for an average of 2.7 years. Results. LIFE’s primary outcome is major mobility disability, defined as the inability to walk 400 m. Secondary outcomes include cognitive function, serious fall injuries, persistent mobility disability, the combined outcome of major mobility disability or death, disability in activities of daily living, and cost-effectiveness. Conclusions. Results of this study are expected to have important public health implications for the large and growing population of older sedentary men and women.

Does the Amount of Fat Mass Predict Age-Related Loss of Lean Mass, Muscle Strength, and Muscle Quality in Older Adults?

Abstract: Background. An excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass and strength with aging. We therefore examined the association of baseline total body fat with changes in leg lean mass, muscle strength, and muscle quality over 7 years of follow-up and whether this link was explained by adipocytokines and insulin resistance. Methods. Data were from 2,307 men and women, aged 70-79 years, participating in the Health, Aging, and Body Composition study. Total fat mass was acquired from dual energy X-ray absorptiometry. Leg lean mass was assessed by dual energy X-ray absorptiometry in Years 1, 2, 3, 4, 5, 6, and 8. Knee extension strength was measured by isokinetic dynamometer in Years 1, 2, 4, 6, and 8. Muscle quality was calculated as muscle strength divided by leg lean mass. Results. Every SD greater fat mass was related to 1.3 kg more leg lean mass at baseline in men and 1.5 kg in women (p < .01). Greater fat mass was also associated with a greater decline in leg lean mass in both men and women (0.02 kg/year, p < .01), which was not explained by higher levels of adipocytokines and insulin resistance. Larger fat mass was related to significantly greater muscle strength but significantly lower muscle quality at baseline (p < .01). No significant differences in decline of muscle strength and quality were found. Conclusions. High fatness was associated with lower muscle quality, and it predicts accelerated loss of lean mass. Prevention of greater fatness in old age may decrease the loss of lean mass and maintain muscle quality and thereby reducing disability and mobility impairments. © The Author 2011. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Relation of Late-Life Social Activity With Incident Disability Among Community-Dwelling Older Adults

Abstract: Background. We tested the hypothesis that a higher level of social activity was associated with decreased risk of incident disability in older adults. Methods. Data came from older adults in the Rush Memory and Aging Project, an ongoing longitudinal cohort study of aging. Analyses were restricted to persons without clinical dementia and reporting no need for help performing any task in the particular functional domain assessed. Participants were followed for an average of 5.1 years (SD = 2.5). Social activity, based on 6 items (visiting friends or relatives; going to restaurants, sporting events, or playing games; group meetings; church/religious services; day or overnight trips; unpaid community/volunteer work), was assessed at baseline. Disability in basic activities of daily living, mobility disability, and instrumental activities of daily living was assessed annually. Proportional hazard models adjusted for age, sex, and education were used to examine the association between social activity and incident disability. Fully adjusted models included terms for depression, vascular diseases and risk factors, body mass index, social networks, and self-reported physical activity. Results. In fully adjusted models, among 954 persons without baseline disability, the risk of developing disability in activities of daily living decreased by 43% (hazard ratio = 0.57, 95% confidence interval = 0.46, 0.71) for each additional unit of social activity. Social activity was also associated with decreased risk of developing mobility disability (hazard ratio = 0.69, 95% confidence interval = 0.54, 0.88) and disability in instrumental activities of daily living (hazard ratio = 0.71, 95% confidence interval = 0.55, 0.93).

Longitudinal versus Cross-sectional Evaluations of Leukocyte Telomere Length Dynamics: Age-Dependent Telomere Shortening is the Rule

Abstract: Background. Leukocyte telomere length (LTL) is considered a biomarker of human aging and based on crosssectional studies it shortens with age. However, longitudinal studies reported that many adults display LTL lengthening. Methods. Using Southern blots, we compared cross-sectional rates of age-related LTL change across a ~20 year age range with those based on longitudinal evaluations in three surveys (S1, S2, and S3) with three time intervals: S1–S2 (5.8 years), S2–S3 (6.6 years), and S1–S3 (12.4 years). Hierarchical linear modeling was used to explore LTL dynamics using LTL data from S1, S2, and S3. Results. Cross-sectionally, mean LTL shortenings were 24.6, 25.4, and 23.6 bp/y at S1, S2, and S3, respectively. Longitudinally, more variation was observed in the rate of LTL change during the shorter than longer follow-up periods. Furthermore, using simple differences in LTL, 14.4% and 10.7% of individuals displayed LTL lengthening during S1– S2 and S2–S3, respectively, but only 1.5% during S1–S3 (p < 0.001). The estimated mean rate of LTL shortening based on averaging empirical Bayes’ estimates of LTL from a parsimonious hierarchical linear modeling model was 31 bp/y with a range from 23 to 47 bp/y with none of the participants showing LTL lengthening over the average 12.4 years of follow-up.

The Relationship of Aspiration Status With Tongue and Handgrip Strength in Healthy Older Adults

Abstract: Background. Recently, subclinical aspiration has been identified in approximately 30% of community-dwelling older adults. Given that the tongue is a key component of the safe swallow, we hypothesized healthy older adults who aspirate will generate less tongue strength than adults who do not aspirate. Furthermore, as muscle weakness may reflect a global effect of aging, we further investigated whether tongue strength is correlated with handgrip strength.

Age-Associated Vascular Oxidative Stress, Nrf2 Dysfunction, and NF-κB Activation in the Nonhuman Primate Macaca mulatta

Abstract: Aging promotes oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of cardiovascular diseases. NF-E2-related factor 2 (Nrf2) is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals, leading to adaptive upregulation of numerous reactive oxygen species detoxifying and antioxidant genes. The present study was designed to elucidate age-associated changes in the homeostatic role of Nrf2-driven free radical detoxification mechanisms in the vasculature of nonhuman primates. We found that carotid arteries of aged rhesus macaques (Macaca mulatta, age: ≥20 years) exhibit significant oxidative stress (as indicated by the increased 8-iso-PGF2α and 4-HNE content and decreased glutathione and ascorbate levels) as compared with vessels of young macaques (age:~10 years) that is associated with activation of the redox-sensitive proinflammatory transcription factor, nuclear factor-kappaB. However, age-related oxidative stress does not activate Nrf2 and does not induce Nrf2 target genes (NQO1, GCLC, and HMOX1). In cultured vascular smooth muscle cells (VSMCs) derived from young M mulatta, treatment with H(2)O(2) and high glucose significantly increases transcriptional activity of Nrf2 and upregulates the expression of Nrf2 target genes. In contrast, in cultured vascular smooth muscle cells cells derived from aged macaques, H(2)O(2)- and high glucose-induced Nrf2 activity and Nrf2-driven gene expression are blunted. High glucose-induced H(2)O(2) production was significantly increased in aged vascular smooth muscle cells compared with that in vascular smooth muscle cells from young M mulatta. Taken together, aging is associated with Nrf2 dysfunction in M mulatta arteries, which likely exacerbates age-related cellular oxidative stress, promoting nuclear factor-kappaB activation and vascular inflammation in aging.

Sex Differences in Age Trajectories of Physiological Dysregulation: Inflammation, Metabolic Syndrome, and Allostatic Load

Abstract: There is a paucity of knowledge from population data about sex differences and their age variation in physiological determinants of longevity. This study fills this gap using nationally representative samples of 38,000 individuals aged 17+ from the National Health and Nutrition Examination Survey (1988-2006). It examines sex differences in the age trajectories of 14 markers of physiological functions across multiple systems and three summary indices including inflammation burden, metabolic syndrome, and allostatic load. Statistical analyses show substantial sex differences, age variations, and sex by age interaction effects for all variables examined. These patterns remain robust after adjustment of risk factors and shed light on the biological base of the reduction of sex difference in mortality in the post-reproductive life span.

Gait Variability Is Associated With Frailty in Community-dwelling Older Adults

Abstract: Background. The relationship between frailty and gait characteristics other than velocity has received little attention. Gait variability quantifies the automaticity of gait with greater variability usually indicating an irregular and unstable gait. High gait variability reflects the loss of gait regulation and predicts mobility decline and falls, which may reveal systemic vulnerability. Thus, we hypothesize that high gait variability may be associated with frailty phenotype. Methods. Cross-sectional study including 100 community-dwelling women and men 75 years and older. Frailty was defined using validated phenotypic criteria and two additional frailty indexes that omit gait velocity criterion were used to verify associations between frailty and quantitative gait parameters. Gait was assessed under usual and fast pace using an electronic walkway. Results. Frailty phenotype was identified in 20% of the participants and at least one component of frailty was present in 75%. Linear regression models were generated to explore the associations between frailty and gait variability. In the univariate regression model, frailty was associated with higher variability for all the gait parameters of interest. After adjustments, stride time variability under fast gait condition was the most prominent parameter consistently associated with frailty. This association remained significant in two additional frailty indexes that omit gait velocity criterion. Conclusion. Frailty is associated with low performance in several quantitative gait parameters beyond velocity of which the most prominent is high stride time variability. This finding may help to understand the high risk of falls and mobility decline in people with frailty.

Plasma Klotho and Mortality Risk in Older Community-Dwelling Adults

Abstract: Methods. We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Results. During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho ( 763 pg/mL; hazards ratio 1.78, 95% confidence interval 1.20–2.63). Conclusions. In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.

Design and Conduct of the CALERIE Study: Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy

Abstract: Background. In a robust and consistent manner, sustained caloric restriction (CR) has been shown to retard the aging process in a variety of animal species. Nonhuman primate studies suggest that CR may have similar effects in longer-lived species. The CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy) research program is the first systematic investigation of CR in non obese human beings. In the phase 2 study, it is hypothesized that 2 years of sustained CR, involving a 25% reduction of ad libitum energy intake, results in beneficial effects similar to those observed in animal studies. This article presents the design and implementation of this study. Methods. The study is a multicenter, parallel-group, randomized controlled trial. A sample of 225 participants (22.0 ≤ body mass index [BMI] < 28.0 kg/m 2 ) is being enrolled with 2:1 allocation to CR. Results. An intensive dietary and behavioral intervention was developed to achieve 25% CR and sustain it over the 2 years. Adherence is monitored using a doubly labeled water technique. Primary outcomes are resting metabolic rate and core temperature, and are assessed at baseline and at 6-month intervals. Secondary outcomes address oxyradical formation, cardiovascular risk markers, insulin sensitivity and secretion, immune function, neuroendocrine function, quality of life and cognitive function. Biologic materials are stored in a central repository. Conclusions. An intricate protocol has been developed to conduct this study. Procedures have been implemented to safeguard the integrity of the data and the conclusions drawn. The results will provide insight into the detrimental changes associated with the human aging process and how CR mitigates these effects.

Vitamin D and cognitive impairment in the elderly U.S. population.

Abstract: VITAMIN D may be neuroprotective as it influences neurogenesis, calcium homeostasis, the expression of neurotrophic factors, detoxification, and amyloid-beta clearance (1–3). Recent population-based studies have linked low serum 25-hydroxyvitamin D (25(OH)D) levels to cognitive dysfunction in older adults in England (4) and across Europe (5). However, the evidence from studies in the United States is less consistent. Low 25(OH)D levels were associated with cognitive dysfunction in homebound elderly adults from Boston (6). However, those with the highest levels of serum 25(OH)D were more likely to be impaired on a test of delayed verbal memory in older U.S. adults from the Third National Health and Nutrition Examination Survey (NHANES III) (7). We hypothesized that the inconsistency between the results from NHANES III and other studies might reflect the minimal adjustment for potential confounders or the limited use of available cognitive measures. We therefore examined the multivariate adjusted association between vitamin D and cognitive impairment using data from NHANES III.

Validation of an Armband to Measure Daily Energy Expenditure in Older Adults

Abstract: BACKGROUND Objective methods to measure daily energy expenditure in studies of aging are needed. We sought to determine the accuracy of total energy expenditure (TEE) and activity energy expenditure (AEE) estimates from the SenseWear Pro armband (SWA) using software versions 6.1 (SWA 6.1) and 5.1 (SWA 5.1) relative to criterion methods in free-living older adults. METHODS Participants (n = 19, mean age 82.0 years) wore a SWA for a mean ± SD 12.5 ± 1.1 days, including while sleeping. During this same period, criterion values for TEE were assessed with doubly labeled water and for resting metabolic rate (RMR) with indirect calorimetry. AEE was calculated as 0.9 TEE - RMR. RESULTS For TEE, there was no difference in mean ± SD values from doubly labeled water (2,040 ± 472 kcal/day) versus SWA 6.1 (2,012 ± 497 kcal/day, p = .593) or SWA 5.1 (2,066 ± 474 kcal/day, p = .606); individual values were highly correlated between methods (SWA 6.1 r = .893, p < .001; SWA 5.1 r = .901, p < .001) and demonstrated strong agreement (SWA 6.1 intraclass correlation coefficient = .896; SWA 5.1 intraclass correlation coefficient = .904). For AEE, mean values from SWA 6.1 (427 ± 304 kcal/day) were lower by 26.8% than criterion values (583 ± 242 kcal/day, p = .003), and mean values from SWA 5.1 (475 ± 299 kcal/day) were lower by 18.5% than criterion values (p = .021); however, individual values were highly correlated between methods (SWA 6.1 r = .760, p < .001; SWA 5.1 r = .786, p < .001) and demonstrated moderate agreement (SWA 6.1 intraclass correlation coefficient = .645; SWA 5.1 intraclass correlation coefficient = .720). Bland-Altman plots identified no systematic bias for TEE or AEE. CONCLUSIONS Acceptable levels of agreement were observed between SWA and criterion measurements of TEE and AEE in older adults.

Association Between Muscle Activation and Metabolic Cost of Walking in Young and Old Adults

Abstract: Results. Cw was 7.0% (incline), 19.2% (level), and 47.3% (decline) higher in old adults (overall 18.3%). Old (67.1%) versus young (40.1%) adults activated their leg muscles 67.3% more during the gait tasks and had 152.8% higher antagonist muscle coactivation (old: 67.1%, young: 19.9%). Agonist muscle activation was unrelated to Cw on incline, but it explained up to 42% (level), 48% (decline), and 70% (three tasks combined) of variance in Cw. Antagonist coactivation accounted for up to 41% (incline), 45% (level), 59% (decline), 39% (three tasks combined) of variance in Cw. Conclusions. Age-related adaptations in the recruitment pattern of leg muscles during gait significantly contribute to the high Cw in old adults. Clinical interventions optimizing the neural control of leg muscles during gait could reduce Cw consequently the relative effort needed for exercise and activities of daily living in old adults.

The Relationship Between Intervening Hospitalizations and Transitions Between Frailty States

Abstract: INCREASINGLY, frailty is recognized as a geriatric syndrome, distinct from disability and comorbidity, which results from a multisystem reduction in reserve capacity, confers high risk for an array of adverse outcomes, and is potentially amenable to prevention and remediation (1–3). As an indicator of its societal importance, the Institute of Medicine has identified frailty as one of 20 priority areas (selected from several hundred potential candidates) in need for improvement in health care quality (4). In prior work, we have demonstrated that frailty is a dynamic process, characterized by frequent transitions between frailty states (nonfrail, prefrail, and frail) over time (5). These findings have since been confirmed by other investigators (6). The reasons behind these transitions are largely unknown, although numerous studies have evaluated potential risk factors for the initial onset of frailty (7–11). One possibility is that transitions between frailty states are driven, at least in part, by intervening illnesses and injuries leading to hospitalization. These intervening hospitalizations, for example, could impede recovery from states of greater frailty to lesser frailty and, in turn, place older persons at higher risk for subsequent adverse outcomes. In support of this possibility, we have recently shown that hospitalization in older persons has pronounced deleterious effects on nearly all transitions between states of disability over the course of more than 10 years (12). To improve our understanding of frailty among older persons, we set out in the current study to determine the relationship between intervening hospitalizations and transitions between frailty states over time. We hypothesized that transitions from nonfrail to frail would be uncommon in the absence of a hospitalization and that intervening illnesses and injuries leading to hospitalization would reduce the likelihood of transitioning from states of greater frailty to states of lesser frailty (ie, impede recovery).

Validation of New Measures of Disability and Functioning in the National Health and Aging Trends Study

Abstract: Background. Measurement gaps continue to hamper fuller understanding of late-life disability trends and dynamics. This article reports findings that validate the self-reported components of the disability protocol to be used in the new National Health and Aging Trends Study. The protocol was designed to redress existing measures by attending to environmental aspects of disability, capturing a broader range of capacity to perform tasks and including participation restriction items. Methods. We undertook an in-person validation study to determine the reliability, validity, and initial measurement properties of the National Health and Aging Trends Study self-reported disability protocol (n = 326). A random subset (n = 111) was readministered the protocol within 2–4 weeks. The interview and reinterview included new self-reported measures of physical capacity, activity limitations, and participation restrictions, as well as established performance and cognitive tests. We calculated percent agreement and kappa between interviews for all self-reported items and summary measures. We also assessed the construct validity of summary measures through correlations with demographic characteristics, frailty, memory, and performance-based mobility and confirmed whether activity limitations and participation restrictions were distinct domains. Results. New items and derived summary measures demonstrate robustness over a short time period, with kappas for retained/recommended items in the .60–.80 range. The summary measures correlate as expected with age, sex, residential status, and established performance-based constructs. Two factors, representing activity limitations and participation restrictions, were confirmed. Conclusions. The National Health and Aging Trends Study protocol preserves the ability to examine more traditional measures of functioning while offering new insights into how activities are performed and preserving key conceptual distinctions.

Increases in Thigh Muscle Volume and Strength by Walk Training with Leg Blood Flow Reduction in Older Participants

Abstract: We examined the effects of walk training combined with leg blood flow reduction (BFR) on muscle hypertrophy as well as on peak oxygen uptake (VO₂ peak) in older individuals. Both the BFR walk training (BFR-Walk, n = 10, age; 64 ± 1 years, body mass index [BMI]; 22.5 ± 0.9 kg/m²) and control walk training (CON-Walk, n = 8, age; 68 ± 1 years, BMI; 23.2 ± 1.0 kg/m²) groups performed 20 minutes of treadmill walking at an exercise intensity of 45% of heart rate reserve, 4 days per week, for 10 weeks. The BFR-Walk group wore pressure belts (160-200 mm Hg) on both legs during training. After the training, magnetic resonance imaging-measured thigh muscle cross-sectional area (3.1%, p < .01) and muscle volume (3.7%, p < .01) as well as maximal isometric (5.9%, p < .05) and isokinetic (up to 22%, p < .01) strength increased in the BFR-Walk group, but not in the CON-Walk group. Estimated VO₂ peak during a bicycle graded exercise test increased (p < .05) and correlated with oxygen pulse in both groups. In conclusion, BFR walk training improves both muscle volume and strength in older women.

Inflammatory Markers and Gait Speed Decline in Older Adults

Abstract: Background. Increased inflammatory activity and gait speed decline are common with aging, but the association between the two is not well established. The objective of this study was to determine the influence of inflammatory markers, interleukin-6 (IL-6), and tumor necrosis factor alpha, on gait speed performance and decline in older adults. Methods. We conducted cross-sectional and longitudinal analyses of 333 adults aged 70 and older (61% women) with gait and biomarker assessments identified from participants in the Einstein Aging Study, a community-based aging study. Gait velocity measured at baseline and annual follow-up visits (median follow-up 2.3 years) was the main outcome. Results. At baseline, higher interleukin-6 levels were associated with slower gait velocity (estimate −4.90 cm/s, p = .008). Adjusted for age, gender, education, and medical illnesses, a one-unit increase in baseline log IL-6 levels was associated with a 0.98 cm/s faster gait speed decline per year (p = .002). The results remained significant after adjustments for additional potential confounders such as physical activity levels, body mass index, and medications. Participants in the highest IL-6 quartile had a 1.75 cm/s/year faster decline in gait velocity compared with those in the lowest quartile (p = .002). Tumor necrosis factor alpha was not associated with gait velocity at cross-section or with gait speed decline. Conclusions. IL-6 levels are associated with gait performance in community residing seniors and predicts risk of gait

Long-Term Supplementation With Resveratrol Alleviates Oxidative Stress but Does Not Attenuate Sarcopenia in Aged Mice

Abstract: This study analyzed the capacity of resveratrol, a naturally occurring polyphenol, to reduce aging-induced oxidative stress and protect against sarcopenia. Middle-aged (18 months) C57/BL6 mice were randomly assigned to receive either a control diet or a diet supplemented with 0.05% trans-resveratrol for 10 months. Young (6 months) and middle-aged (18 months) mice were used as controls. Resveratrol supplementation did not reduce the aging-associated loss of muscle mass or improve maximal isometric force production, but it appeared to preserve fast-twitch fiber contractile function. Resveratrol supplementation did not improve mitochondrial content, the subcellular localization of cytochrome c protein content, or PGC1 protein content. Resveratrol increased manganese superoxide dismutase (MnSOD), reduced hydrogen peroxide, and lipid peroxidation levels in muscle samples, but it was unable to significantly reduce protein carbonyl levels. The data suggest that resveratrol has a protective effect against aging-induced oxidative stress in skeletal muscle, likely through the upregulation of MnSOD activity, but sarcopenia was not attenuated by resveratrol.

Validation of a Measure of Smoothness of Walking

Abstract: SMOOTHNESS is a measure of the rhythmic pattern of acceleration and deceleration of the trunk during walking (1). Smoothness of walking is a function of the integration of the kinematics, kinetics, and the coordination (neural control) of gait. Common problems of gait in older adults, such as abnormalities of posture, postural reflexes, muscle function, and the timing and coordination of posture with the phases of gait, result in a loss of the smooth forward progression of walking (2–4). For example, a lack of hip extension during gait can disrupt the coordination of heel strike of the leading limb with push-off of the trailing limb, a feature of gait that facilitates forward progression of the body, whereas the leading limb transitions from forward to backward movement in the step cycle. A disruption of the coordination of heel strike and push-off can mean prolonged deceleration of the leading limb at heel strike and altered accelerations of the trunk to advance the trailing limb (5,6). Such age-related changes in gait would most likely be associated with slowing of gait speed; however, a measure of gait speed would not represent the changes in the smoothness of walking. Thus, gait speed measures do not differentiate those who walk slowly but with a “good” pattern of walking from those who walk slowly with marked abnormalities of the mechanics and timing of gait. Measures of gait variability have added to the recognition of age-related abnormalities of gait beyond slow speed alone (7); however, quantitative measures of gait variability focus primarily on the lower extremities and the steps of the individual and limit gait assessment to gait laboratory-like settings, with instrumented walkways typical of research settings. Smoothness of walking, calculated as the harmonic ratio of the trunk acceleration signals collected using a triaxial accelerometer, takes into account the whole body and not just the steps of the lower extremity and can be collected in the clinic and in usual naturalistic settings for walking and is not limited to gait laboratory environments (8,9). Smoothness of walking has been examined in limited groups of individuals and under very few walking conditions. Older adults, who likely have impaired gait biomechanics and neural control (9,10), individuals with Parkinson’s disease (11), and individuals with sensory impairment (12) are less smooth in walking than young adults or individuals without disease. Walking speed is known to affect smoothness of walking. In a sample of young (age range: 22–39 years) healthy adults, walking speed was shown to influence smoothness of walking; self-selected walking speed was the most smooth, whereas slower speeds affected smoothness more than faster speeds (1). The goal of this work was to further develop the harmonic ratio of trunk acceleration series as a measure of smoothness of walking. Specifically, the purpose was to validate the harmonic ratio by examining groups expected to differ in smoothness (ie, young and old) and across challenging walking conditions expected to affect smoothness (ie, usual pace straight path, slow pace straight path, curved path, and dual task). We hypothesize that older adults will be less smooth than young adults and that slow pace, curved path, and dual task walking will be less smooth than usual pace straight path walking. We also explored the impact of age on smoothness of walking independent of gait speed by examining three groups: young, older adults with gait speed similar to the young adults, and older adults who walk slowly.

Association between Obesity History and Hand Grip Strength in Older Adults—Exploring the Roles of Inflammation and Insulin Resistance as Mediating Factors

Abstract: Results Earlier onset of obesity was associated with lower hand grip strength (p < 001) after controlling for age, sex, education, smoking, alcohol use, physical activity, several chronic diseases, and current body weight Based on adjusted logistic regression models, the odds (95% confidence interval) for very low relative hand grip strength were 276 (178–428) for currently obese, 557 (302–1028) for obese since age of 50 years, 653 (298–1430) for obese since age of 40 years, and 1036 (355–3024) for obese since age of 30 years compared with never obese participants The associations remained highly significant even after adjusting for current C-reactive protein and HOMA-IR, but these variables had only minor role in explaining the association between obesity history and hand grip strength Conclusions Long-term exposure to obesity is associated with poor hand grip strength later in life Maintaining healthy body weight throughout the life span may help to maintain adequate muscle strength in old age Prospective studies with information on prior muscle strength are needed to examine in detail the causal association between obesity history and muscle strength