Abstract
Background
Body composition assessment by computed tomography (CT) predicts health outcomes in diverse populations. However, its performance in predicting mortality has not been directly ...compared to dual-energy X-ray absorptiometry (DXA). Additionally, the association between different body compartments and mortality, acknowledging the compositional nature of the human body, is not well studied. Compositional data analysis, which is applied to multivariate proportion-type data set, may help to account for the interrelationships of body compartments by constructing log ratios of components. Here, we determined the associations of baseline CT-based measures of mid-thigh cross-sectional areas versus DXA measures of body composition with all-cause mortality in the Health ABC cohort, using both traditional (individual body compartments) and compositional data analysis (using ratios of body compartments) approaches.
Methods
The Health ABC study assessed body composition in 2911 older adults in 1996–1997. We investigated the individual and ratios of (by compositional analysis) body compartments assessed by DXA (lean, fat, and bone masses) and CT (muscle, subcutaneous fat area, intermuscular fat, and bone) on mortality, using Cox proportional hazard models.
Results
Lower baseline muscle area by CT (hazard ratio HRmen = 0.56; 95% confidence interval 95% CI: 0.48–0.67, HRwomen = 0.60; 95% CI: 0.48–0.74) and fat mass by DXA (HRmen = 0.48; 95% CI: 0.24–0.95) were predictors of mortality in traditional Cox regression analysis. Consistently, compositional data analysis revealed that lower muscle area versus IMF, muscle area versus bone area, and lower fat mass versus lean mass were associated with higher mortality in both sexes.
Conclusion
Both CT measure of muscle area and DXA fat mass (either individually or relative to other body compartments) were strong predictors of mortality in both sexes in a community research setting.
Abstract
Background
Age-related deposition of fat in skeletal muscle is associated with functional limitations. Skeletal muscle fat may be present in people with preserved muscle mass or accompanied ...by muscle wasting. However, it is not clear if the association between muscle fat deposition and physical performance is moderated by muscle mass.
Objective
To determine whether the association between midthigh intermuscular fat and physical performance is moderated by muscle area.
Methods
We performed a cross-sectional analysis of the Health, Aging, and, Body Composition (ABC) study data collected in 2002–2003 (n = 1897, women: 52.2%). Midthigh muscle cross-sectional area (by computed tomography) and physical performance measures were compared across quartiles of intermuscular fat absolute area. Moderation analysis was performed to determine the conditional effect of intermuscular fat on physical performance as a function of muscle area. Conditional effects were evaluated at three levels of muscle area (mean and ± 1 standard deviation SD; 213.2 ± 53.2 cm2).
Results
Simple slope analysis showed that the negative association between intermuscular fat area (cm2) and leg strength (N·m) was of greater magnitude (beta coefficient b, 95% confidence interval CI = −0.288 −0.427, −0.148) in participants with greater muscle area (ie, 1 SD above the mean) compared to those with lower muscle area (ie, at mean b = −0.12 {−0.248, 0.008} or 1 SD below the mean b = 0.048 {−0.122, 0.217}). Similarly, the negative association of intermuscular fat with 400-m walk speed (m/s) and chair stand (seconds) was greater in those with higher muscle areas (p < .001) compared to those with lower muscle areas.
Conclusions
The association between higher intermuscular fat area and impaired physical function in aging is moderated by muscle area.
Fatigability is a construct that measures whole-body tiredness anchored to activities of a fixed intensity and duration; little is known about its epidemiology and heritability.
Two generations of ...family members enriched for exceptional longevity and their spouses were enrolled (2006-2009) in the Long Life Family Study (LLFS). At Visit 2 (2014-2017, N = 2,355) perceived physical fatigability was measured using the 10-item self-administered Pittsburgh Fatigability Scale (PFS), along with demographic, medical, behavioral, physical, and cognitive risk factors.
Residual genetic heritability of fatigability was 0.263 (p = 6.6 × 10-9) after adjustment for age, sex, and field center. PFS physical scores (mean ± SD) and higher physical fatigability prevalence (% PFS ≥ 15) were greater with each age strata: 60-69 (n = 1,009, 11.0 ± 7.6, 28%), 70-79 (n = 847, 12.5 ± 8.1, 37%), 80-89 (n = 253, 19.3 ± 9.9, 65.2%), and 90-108 (n = 266, 28.6 ± 9.8, 89.5%), p < .0001, adjusted for sex, field center, and family relatedness. Women had a higher prevalence of perceived physical fatigability compared to men, with the largest difference in the 80-89 age strata, 74.8% versus 53.5%, p < .0001. Those with greater body mass index, worse physical and cognitive function, and lower physical activity had significantly higher perceived physical fatigability.
Perceived physical fatigability is highly prevalent in older adults and strongly associated with age. The family design of LLFS allowed us to estimate the genetic heritability of perceived physical fatigability. Identifying risk factors associated with higher perceived physical fatigability can inform the development of targeted interventions for those most at risk, including older women, older adults with depression, and those who are less physically active.
Abstract
Background
Mitochondrial energetics are an important property of aging muscle, as generation of energy is pivotal to the execution of muscle contraction. However, its association with ...functional outcomes, including leg power and cardiorespiratory fitness, is largely understudied.
Methods
In the Study of Muscle, Mobility, and Aging, we collected vastus lateralis biopsies from older adults (n = 879, 70–94 years, 59.2% women). Maximal State 3 respiration (Max OXPHOS) was assessed in permeabilized fiber bundles by high-resolution respirometry. Capacity for maximal adenosine triphosphate production (ATPmax) was measured in vivo by 31P magnetic resonance spectroscopy. Leg extension power was measured with a Keiser press system, and VO2 peak was determined using a standardized cardiopulmonary exercise test. Gender-stratified multivariate linear regression models were adjusted for age, race, technician/site, adiposity, and physical activity with beta coefficients expressed per 1-SD increment in the independent variable.
Results
Max OXPHOS was associated with leg power for both women (β = 0.12 Watts/kg, p < .001) and men (β = 0.11 Watts/kg, p < .050). ATPmax was associated with leg power for men (β = 0.09 Watts/kg, p < .05) but was not significant for women (β = 0.03 Watts/kg, p = .11). Max OXPHOS and ATPmax were associated with VO2 peak in women and men (Max OXPHOS, β women = 1.03 mL/kg/min, β men = 1.32 mL/kg/min; ATPmax β women = 0.87 mL/kg/min, β men = 1.50 mL/kg/min; all p < .001).
Conclusions
Higher muscle mitochondrial energetics measures were associated with both better cardiorespiratory fitness and greater leg power in older adults. Muscle mitochondrial energetics explained a greater degree of variance in VO2 peak compared to leg power.
Pulmonary function (PF) progressively declines with aging. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) are predictors of morbidity of pulmonary and ...cardiovascular diseases and all-cause mortality. In addition, reduced PF is associated with elevated chronic low-grade systemic inflammation, glucose metabolism, body fatness, and low muscle strength. It may suggest pleiotropic genetic effects between PF with these age-related factors.
We evaluated whether FEV1 and FVC share common pleiotropic genetic effects factors with interleukin-6, high-sensitivity C-reactive protein, body mass index, muscle (grip) strength, plasma glucose, and glycosylated hemoglobin in 3,888 individuals (age range: 26-106). We employed sex-combined and sex-specific correlated meta-analyses to test whether combining genome-wide association p-values from two or more traits enhances the ability to detect variants sharing effects on these correlated traits.
We identified 32 loci for PF, including 29 novel pleiotropic loci associated with pulmonary function and (i) body fatness (CYP2U1/SGMS2), (ii) glucose metabolism (CBWD1/DOCK8 and MMUT/CENPQ), (iii) inflammatory markers (GLRA3/HPGD, TRIM9, CALN1, CTNNB1/ZNF621, GATA5/SLCO4A1/NTSR1, and NPVF/C7orf31/CYCS), and (iv) muscle strength (MAL2, AC008825.1/LINC02103, AL136418.1).
The identified genes/loci for PF and age-related traits suggest their underlying shared genetic effects, which can explain part of their phenotypic correlations. Integration of gene expression and genomic annotation data shows enrichment of our genetic variants in lung, blood, adipose, pancreas, and muscles, among others. Our findings highlight the critical roles of identified gene/locus in systemic inflammation, glucose metabolism, strength performance, PF, and pulmonary disease, which are involved in accelerated biological aging.
Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults.
Using genome-wide linkage analysis, we identified a novel locus on chromosome ...18p (mega-basepair region: 3.4 - 4.0) linked to grip strength in 3755 individuals from 582 families aged 64 ± 12 years (range 30-110 years; 55% women). There were 26 families that contributed to the linkage peak (cumulative logarithm of the odds LOD score = 10.94), with six families (119 individuals) accounting for most of the linkage signal (LOD = 6.4). In these 6 families, using whole genome sequencing data, we performed association analyses between the 7312 single nucleotide (SNVs) and insertion deletion (INDELs) variants in the linkage region and grip strength. Models were adjusted for age, age2, sex, height, field center, and population substructure.
We found significant associations between genetic variants (8 SNVs and 4 INDELs, p<5*10-5) in the Disks Large-associated Protein 1 (DLGAP1) gene and grip strength. Haplotypes constructed using these variants explained up to 98.1% of the LOD score. Finally, RNAseq data showed that these variants were significantly associated with the expression of nearby Myosin Light Chain 12A (MYL12A), Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1), Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) genes (p< .0004).
The DLGAP1 gene plays an important role in the post-synaptic density of neurons; thus, it is both a novel positional and biological candidate gene for follow-up studies aimed at uncovering genetic determinants of muscle strength.
Abstract
Background
Sarcopenia varies by ethnicity, and has a major impact on health in older adults. However, little is known about sarcopenia characteristics in African ancestry populations outside ...the United States. We examined sarcopenia characteristics in 2,142 African Caribbean men aged 59.0 ± 10.4 years (range: 40–92 years) in Tobago, and their association with incident mobility limitations in those aged 55+ (n = 738).
Methods
Body mass index (BMI), grip strength, dual-x-ray absorptiometry (DXA) appendicular lean mass (ALM), and self-reported mobility limitations were measured at baseline, and 6 years later. Change in sarcopenia characteristics, including grip strength, grip strength/BMI, ALMBMI, and ALM/ht2, were determined. Foundations for the National Institutes of Health Sarcopenia Project (FNIH) and European Working Group for Sarcopenia in Older People 2 (EWGSOP2) cut-points were also examined. Odds ratios (OR) and 95% confidence intervals (CI) for mobility limitation were calculated using multivariable linear regression models adjusted for covariates.
Results
Overall, sarcopenia prevalence was quite low using the FNIH (0.3%) and EWGSOP2 (0.6%) operational cut-points, but was higher in those aged 75+ (2.1% FNIH and 3.7% EWGSOP2). Prevalence was also higher when based on “weakness”, versus “low ALM.” When sarcopenia markers were examined separately, baseline levels, but not changes, were associated with incident mobility limitations. Baseline grip strength/BMI was a particularly strong risk factor for incident mobility limitations (OR per SD: 0.50; 95% CI: 0.37–0.68).
Conclusions
Our findings suggest that grip strength normalized to body mass, measured at one time point, may be a particularly useful phenotype for identifying African Caribbean men at risk for future mobility limitations.
Abstract
Background
Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. Herein, we tested if P3NP was ...associated with baseline and 7-year change in physical function.
Method
Participants (n = 400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay coefficient of variation <5.5%). At baseline and 7-year follow-up visits, physical function was measured using the Short Physical Performance Battery (SPPB score 0–12), which consists of gait speed, balance, and chair-rise tests. Grip strength was measured using a handheld dynamometer. The association between log-transformed P3NP and physical function was examined using generalized estimating equations adjusted for familial relatedness, age, sex, height, weight, lifestyle characteristics, liver function, kidney function, lung function, and chronic disease prevalence.
Results
Participants were aged 73.1 ± 15.2 years (range: 39–104), 54% female, had body mass index of 26.6 ± 4.3 kg/m2, and gait speeds of 1.0 ± 0.3 m/s. One standard deviation higher log-transformed P3NP was related to worse baseline SPPB score (β = −0.9points), gait speed (β = −0.05m/s), chair-rises per-second (β = −0.46chair-rises/10 seconds), and grip strength (β = −2.0kg; all p < .001). Higher P3NP was also associated with greater declines in gait speed (β = −1.41, p < .001) and transitioning to being unable to perform chair-rises (β = 0.41, p < .001) after 7 years.
Conclusion
Plasma P3NP may be a strong, novel biomarker of current and future physical function. Future research is needed to extend our findings to other cohorts and determine mechanisms underlying these associations.
BACKGROUND/OBJECTIVES
The extent to which the prevalence of muscle weakness in the US population varies by different putative grip strength constructs developed by the Sarcopenia Definitions and ...Outcomes Consortium (SDOC) has not been described.
DESIGN
Cross‐sectional analysis.
SETTING
Two nationally representative cohorts—2010 and 2012 waves of the Health and Retirement Survey and round 1 (2011) of the National Health and Aging Trends Survey.
PARTICIPANTS
Adults aged 65 years and older (n = 12,984) were included in these analyses.
MEASUREMENTS
We analyzed three constructs of muscle weakness developed by the SDOC, and found to be associated with mobility disability for men and women, respectively: absolute grip strength (<35.5 kg and 20 kg); grip strength standardized to body mass index (<1.05 kg/kg/m² and 0.79 kg/kg/m²); and grip strength standardized to weight (<0.45 kg/kg and 0.337 kg/kg). We estimated the prevalence of muscle weakness defined by each of these constructs in the overall older US population, and by age, sex, race, and ethnicity. We also estimated the sensitivity and specificity of each of the grip strength constructs to discriminate slowness (gait speed <0.8 m/s) in these samples.
RESULTS
The prevalence of muscle weakness ranged from 23% to 61% for men and from 30% to 66% for women, depending on the construct used. There was substantial variation in the prevalence of muscle weakness by race and ethnicity. The sensitivity and specificity of these measures for discriminating slowness varied widely, ranging from 0.30 to 0.92 (sensitivity) and from 0.17 to 0.88 (specificity).
CONCLUSIONS
The prevalence of muscle weakness, defined by the putative SDOC grip strength constructs, depends on the construct of weakness used. J Am Geriatr Soc 68:1438‐1444, 2020.
See related editorial by Cesari et al in this issue
ABSTRACT
Introduction
Efforts to study performance fatigability have been limited because of measurement constrains. Accelerometry and advanced statistical methods may enable us to quantify ...performance fatigability more granularly via objective detection of performance decline. Thus, we developed the Pittsburgh Performance Fatigability Index (PPFI) using triaxial raw accelerations from wrist-worn accelerometer from two in-laboratory 400-m walks.
Methods
Sixty-three older adults from our cross-sectional study (mean age, 78 yr; 56% women; 88% White) completed fast-paced (
n
= 59) and/or usual-paced 400-m walks (
n
= 56) with valid accelerometer data. Participants wore ActiGraph GT3X+ accelerometers (The ActiGraph LLC, Pensacola, FL) on nondominant wrist during the walking task. Triaxial raw accelerations from accelerometers were used to compute PPFI, which quantifies percentage of area under the observed gait cadence-versus-time trajectory during a 400-m walk to a hypothetical area that would be produced if the participant sustained maximal cadence throughout the entire walk.
Results
Higher PPFI scores (higher score = greater fatigability) correlated with worse physical function, slower chair stands speed and gait speed, worse cardiorespiratory fitness and mobility, and lower leg peak power (|
ρ
| = 0.36–0.61 from fast-paced and |
ρ
| = 0.28–0.67 from usual-paced walks, all
P
< 0.05). PPFI scores from both walks remained associated with chair stands speed, gait speed, fitness, and mobility, after adjustment for sex, age, race, weight, height, and smoking status; PPFI scores from the fast-paced walk were associated with leg peak power.
Conclusions
Our findings revealed that the objective PPFI is a sensitive measure of performance fatigability for older adults and can serve as a risk assessment tool or outcome measure in future studies and clinical practice.
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