Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically ...relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts.
The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups.
The pooled sample included 26,625 participants (57% women, mean age in men 75.2 ±6.1 SD and in women 78.6 ±5.9 years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women.
These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.
BACKGROUND: Sarcopenia is thought to be accompanied by increased muscle fat infiltration. However, no longitudinal studies have examined concomitant changes in muscle mass, strength, or fat ...infiltration in older adults. OBJECTIVE: We present longitudinal data on age-related changes in leg composition, strength, and muscle quality (MQ) in ambulatory, well-functioning men and women. We hypothesized that muscle cross-sectional area (CSA) and strength would decrease and muscular fat infiltration would increase over 5 y. DESIGN: Midthigh muscle, subcutaneous fat (SF), and intermuscular fat (IMF) CSAs and isokinetic leg muscle torque (MT) and MQ (MT/quadriceps CSA) were examined over 5 y in the Health, Aging, and Body Composition study cohort (n = 1678). RESULTS: Men experienced a 16.1% loss of MT, whereas women experienced a 13.4% loss. Adjusted annualized decreases in MT were 2-5 times greater than the loss of muscle CSA in those who lost weight and in those who remained weight-stable. Weight gain did not prevent the loss of MT, despite a small increase in muscle CSA. Only those who gained weight had an increase in SF (P < 0.001), whereas those who lost weight also lost SF (P < 0.001). There was an age-related increase in IMF in men and women (P < 0.001), and IMF increased in those who lost weight, gained weight, or remained weight-stable (all P < 0.001). CONCLUSIONS: Loss of leg MT in older adults is greater than muscle CSA loss, which suggests a decrease in MQ. Additionally, aging is associated with an increase in IMF regardless of changes in weight or SF.
Introduction Tobacco use remains a leading modifiable cause of cancer incidence and premature mortality in the U.S. and globally. Despite increasing life expectancy worldwide, less is known about the ...effects of cigarette smoking on older populations. This study sought to determine the effects of smoking on mortality in older age. Methods Associations of mortality with self-reported age at smoking cessation, age at smoking initiation, and amount smoked after age 70 years were examined in 160,113 participants of the NIH-AARP Diet and Health Study aged >70 years. Participants completed a questionnaire detailing their smoking use in 2004–2005, and were followed for mortality through December 31, 2011. Analyses were conducted between 2014 and 2016. Results Relative to never smokers, current smokers were more likely to die during follow-up (hazard ratio, 3.18; 95% CI=3.04, 3.31). Furthermore, former smokers had lower risks than current smokers (hazard ratios for quitting between ages 30–39, 40–49, 50–59, and 60–69 years were 0.41 95% CI=0.39, 0.43, 0.51 95% CI=0.49, 0.54, 0.64 95% CI=0.61, 0.67, and 0.77 95% CI=0.73, 0.81, respectively). Among current smokers, mortality was inversely associated with age at initiation, but directly associated with the number of cigarettes smoked per day at age >70 years. Conclusions As among younger people, lifetime cigarette smoking history is a key determinant of mortality after age 70 years.
Objective The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. Background Frailty is common in the elderly and is associated with ...adverse health outcomes. Impact of frailty on HF risk is not known. Methods We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. Results Mean age of participants was 74 ± 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). Conclusions Frailty is independently associated with risk of HF in older adults.
Introduction Accelerometers are used increasingly in large epidemiologic studies, but, given logistic and cost constraints, most studies are restricted to a single, 7-day accelerometer monitoring ...period. It is unknown how well a 7-day accelerometer monitoring period estimates longer-term patterns of behavior, which is critical for interpreting, and potentially improving, disease risk estimates in etiologic studies. Methods A subset of participants from the Women’s Health Study (N=209; mean age, 70.6 SD=5.7 years) completed at least two 7-day accelerometer administrations (ActiGraph GT3X+) within a period of 2–3 years. Monitor output was translated into total counts, steps, and time spent in sedentary, light-intensity, and moderate to vigorous–intensity activity (MVPA) and bouted-MVPA (i.e., 10-minute bouts). For each metric, intraclass correlations (ICCs) and 95% CIs were calculated using linear-mixed models and adjusted for wear time, age, BMI, and season. The data were collected in 2011–2015 and analyzed in 2015–2016. Results The ICCs ranged from 0.67 (95% CI=0.60, 0.73) for bouted-MVPA to 0.82 (95% CI=0.77, 0.85) for total daily counts and were similar across age, BMI, and for less and more active women. For all metrics, classification accuracy within 1 quartile was >90%. Conclusions These data provide reassurance that a 7-day accelerometer-assessment protocol provides a reproducible (and practical) measure of physical activity and sedentary time. However, ICCs varied by metric; therefore, future prospective studies of chronic diseases might benefit from existing methods to adjust risk estimates for within-person variability in activity to get a better estimate of the true strength of association.
Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA). Previous studies have shown self-reported sedentary time to be associated ...with mortality; however, no studies have investigated the effect of objectively measured sedentary time on mortality independent of MVPA. The objective our study was to examine the association between objectively measured sedentary time and all-cause mortality.
7-day accelerometry data of 1906 participants aged 50 and over from the U.S. nationally representative National Health and Nutrition Examination Survey (NHANES) 2003-2004 were analyzed. All-cause mortality was assessed from the date of examination through December 31, 2006.
Over an average follow-up of 2.8 years, there were 145 deaths reported. In a model adjusted for sociodemographic factors, lifestyle factors, multiple morbidities, mobility limitation, and MVPA, participants in third quartile (hazard ratio (HR):4.05; 95%CI:1.55-10.60) and fourth quartile (HR:5.94; 95%CI: 2.49-14.15) of having higher percent sedentary time had a significantly increased risk of death compared to those in the lowest quartile.
Our study suggests that sedentary behavior is a risk factor for mortality independent of MVPA. Further investigation, including studies with longer follow-up, is needed to address the health consequences of sedentary behavior.
Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low ...impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility - Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = −0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (−0.127 ± 0.037 SD/SD, P<0.001), grey matter (−0.079 ± 0.038 SD/SD, P = 0.038) and white matter (−0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (−0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (−0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (−0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (−0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (−0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.
Age-related losses of lean mass and shifts to central adiposity are related to functional decline and may predict mortality and/or explain part of the risk of weight loss. To determine how mortality ...risk is related to shifts in body composition, changes should be considered in the context of overall weight change.
Five-year changes in body composition were assessed with computed tomography (cm2) and dual x-ray absorptiometry (kg) in 869 men and 934 women initially aged 70-79 years. All-cause mortality was monitored for up to 12 years (2002-2003 to September 30, 2014), and risk was assessed using sex-specific Cox models.
Both men and women lost weight, visceral fat area, thigh muscle area, lean mass, and fat mass (all p < .01) but gained intermuscular thigh fat area (p < .01). There were 995 deaths. After adjustment for total weight change, demographics, and chronic disease, losing thigh muscle area was associated with higher mortality in both men (1.21, 1.08-1.35) and women (1.18, 1.01-1.37, per 9.0cm2) and was especially strong in normal weight (body mass index < 25kg/m2) individuals and those losing weight. Losing intermuscular thigh fat was protective against mortality only in normal weight (0.66, 0.51-0.86) and weight stable men (0.79, 0.66-0.95, per 3.2cm2). Changes in visceral fat area were not associated with mortality.
Older adults with greater loss of thigh muscle than expected for overall weight change had a higher mortality risk compared to those with relative thigh muscle preservation, suggesting that conservation of muscle mass is important for survival in old age.
Objectives
The current Recommended Dietary Allowance (RDA) for protein is based on short‐term nitrogen balance studies in young adults and may underestimate the amount needed to optimally preserve ...physical function in older adults. We examined the association between protein intake and the onset of mobility limitation over 6 years of follow‐up in older adults in the Health ABC study.
Design
Prospective cohort study.
Setting
Memphis, Tennessee and Pittsburgh, Pennsylvania.
Participants
Community‐dwelling, initially well‐functioning adults aged 70–79 years (n = 1998).
Measurements
Protein intake (g/kg body weight/d) was calculated using an interviewer‐administered 108‐item food frequency questionnaire at baseline. Mobility limitation was assessed semi‐annually and defined as reporting any difficulty walking one‐quarter of a mile or climbing 10 steps on 2 consecutive 6‐month contacts. The association between protein intake and incident mobility limitation was examined using Cox proportional hazard regression models adjusting for demographics, behavioral characteristics, chronic conditions, total energy intake, and height.
Results
Mean (SD) protein intake was 0.91 (0.38) g/kg body weight/d, with 43% reporting intakes less than the RDA (0.8 g/kg body weight/d). During 6 years of follow‐up, 705 participants (35.3%) developed mobility limitations. Compared to participants in the upper tertile of protein intake (≥1.0 g/kg body weight/d), participants in the lower two tertiles of protein intake (<0.7 and 0.7 –<1.0 g/kg body weight/d) were at greater risk of developing mobility limitation over 6 years of follow‐up (RR (95% CI): 1.86 (1.41–2.44) and 1.49 (1.20–1.84), respectively).
Conclusion
Lower protein intake was associated with increased risk of mobility limitation in community‐dwelling, initially well‐functioning older adults. These results suggest that protein intakes of ≥1.0 g/kg body weight/d may be optimal for maintaining physical function in older adults.
Epigenetic studies are commonly conducted on DNA from tissue samples. However, tissues are ensembles of cells that may each have their own epigenetic profile, and therefore inter-individual cellular ...heterogeneity may compromise these studies. Here, we explore the potential for such confounding on DNA methylation measurement outcomes when using DNA from whole blood. DNA methylation was measured using pyrosequencing-based methodology in whole blood (n = 50-179) and in two white blood cell fractions (n = 20), isolated using density gradient centrifugation, in four CGIs (CpG Islands) located in genes HHEX (10 CpG sites assayed), KCNJ11 (8 CpGs), KCNQ1 (4 CpGs) and PM20D1 (7 CpGs). Cellular heterogeneity (variation in proportional white blood cell counts of neutrophils, lymphocytes, monocytes, eosinophils and basophils, counted by an automated cell counter) explained up to 40% (p<0.0001) of the inter-individual variation in whole blood DNA methylation levels in the HHEX CGI, but not a significant proportion of the variation in the other three CGIs tested. DNA methylation levels in the two cell fractions, polymorphonuclear and mononuclear cells, differed significantly in the HHEX CGI; specifically the average absolute difference ranged between 3.4-15.7 percentage points per CpG site. In the other three CGIs tested, methylation levels in the two fractions did not differ significantly, and/or the difference was more moderate. In the examined CGIs, methylation levels were highly correlated between cell fractions. In summary, our analysis detects region-specific differential DNA methylation between white blood cell subtypes, which can confound the outcome of whole blood DNA methylation measurements. Finally, by demonstrating the high correlation between methylation levels in cell fractions, our results suggest a possibility to use a proportional number of a single white blood cell type to correct for this confounding effect in analyses.
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