Abstract
Background
African Caribbeans have higher levels of myosteatosis than other populations; however, little is known about the impact of myosteatosis on physical function in African Caribbeans. ...Herein, we examined the association between regional myosteatosis of the calf, thigh, and abdomen versus physical function in 850 African-Ancestry men aged 64.2 ± 8.9 (range 50–95) living on the Caribbean Island of Tobago.
Methods
Myosteatosis was measured using computed tomography and included intermuscular adipose tissue (IMAT) and muscle density levels of the thigh, calf, psoas, and paraspinous muscles. Outcomes included grip strength, time to complete 5 chair-rises, and 4-meter gait speed. Associations were quantified using separate linear models for each myosteatosis depot and were adjusted for age, height, demographics, physical activity, and chronic diseases. Beta coefficients were presented per standard deviation of each myosteatosis depot.
Results
Higher thigh IMAT was the only IMAT depot significantly associated with weaker grip strength (β = −1.3 ± 0.43 kg, p = .003). However, lower muscle density of all 4 muscle groups was associated with weaker grip strength (all p < .05). Calf and thigh myosteatosis (IMAT and muscle density) were significantly associated with both worse chair rise time and gait speed (all p < .05), whereas psoas IMAT and paraspinous muscle density were associated with gait speed.
Conclusion
Myosteatosis of the calf and thigh―but not the abdomen―were strongly associated with grip strength and performance measures of physical function in African Caribbean men. However, posterior abdominal myosteatosis may have some utility when abdominal images are all that are available.
Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of ...fatigability in older adults.
The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol.
ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05).
Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults.
Body composition and muscle strength change vary by age and ethnicity, and have a major impact on health and physical function. Little is known about the patterns of these changes in African-ancestry ...populations. Herein, we examined age-specific (5-year age groups) rates-of-change in lean and fat mass in 1918 African-ancestry men on the Caribbean island of Tobago (baseline age: 62.0±11.8 years, range: 40-99 years). Body composition (DXA) and grip strength were measured at three time points (baseline, 4- and 9-year follow-up). Annualized rates of change were calculated with all 3 time-points using Generalized Estimating Equations. We found that whole body lean mass declined at constant rate until age 65 (-0.72%/year; 95% CI: -0.76, -0.67), which accelerated to -0.92 %/year (-1.02, -0.82) among those 65-69, and again to -1.16 %/year (-1.30, -1.03 ) among those aged 70+. Whole body fat mass increased by a near constant rate of 2.93 %/year (2.72, 3.15%) across the lifespan. Finally, grip strength decline accelerated at age 50, and about 2x faster than lean mass through the lifespan after the age of 50. To conclude, in African-Caribbean men, the acceleration in muscle strength decline precedes the acceleration in lean mass decline by 10-15 years, suggesting decrements in factors other than lean mass drive this initial acceleration in muscle strength decline. We also found that African-Caribbean men undergo a constant shift to a more adipogenic phenotype throughout the adult lifespan (aged 40-99), which likely contributes to age-related loss of muscle and physical function.
Abstract
Background
The Pittsburgh Performance Fatigability Index (PPFI) quantifies the percent decline in cadence using accelerometry during standardized walking tasks. Although PPFI has shown ...strong correlations with physical performance, the developmental sample was relatively homogenous and small, necessitating further validation.
Methods
Participants from the Study of Muscle, Mobility and Aging (N = 805, age = 76.4 ± 5.0 years, 58% women, 85% White) wore an ActiGraph GT9X on the nondominant wrist during usual-paced 400 m walk. Tri-axial accelerations were analyzed to compute PPFI (higher score = greater fatigability). To evaluate construct and discriminant validity, Spearman correlations (rs) between PPFI and gait speed, Short Physical Performance Battery (SPPB), chair stand speed, leg peak power, VO2peak, perceived fatigability, and mood were examined. Sex-specific PPFI cut-points that optimally discriminated gait speed using classification and regression tree were then generated. Their discriminate power in relation to aforementioned physical performance were further evaluated.
Results
Median PPFI score was 1.4% (25th–75th percentile range: 0%–21.7%), higher among women than men (p < .001). PPFI score was moderate-to-strongly correlated with gait speed (rs = −0.75), SPPB score (rs = −0.38), chair stand speed (rs = −0.36), leg peak power (rs = −0.34) and VO2peak (rs = −0.40), and less strongly with perceived fatigability (rs = 0.28–0.29), all p < .001. PPFI score was not correlated with mood (|rs| < 0.08). Sex-specific PPFI cut-points (no performance fatigability: PPFI = 0%; mild performance fatigability: 0% < PPFI < 3.5% women, 0% < PPFI < 5.4% men; moderate-to-severe performance fatigability: PPFI ≥ 3.5% women, PPFI ≥ 5.4% men) discriminated physical performance (all p < .001), adjusted for demographics and smoking status.
Conclusion
Our work underscores the utility of PPFI as a valid measure to quantify performance fatigability in future longitudinal epidemiologic studies and clinical/pharmaceutical trials.
Performance fatigability is typically experienced as insufficient energy to complete daily physical tasks, particularly with advancing age, often progressing toward dependency. Thus, understanding ...the etiology of performance fatigability, especially cellular‐level biological mechanisms, may help to delay the onset of mobility disability. We hypothesized that skeletal muscle energetics may be important contributors to performance fatigability. Participants in the Study of Muscle, Mobility and Aging completed a usual‐paced 400‐m walk wearing a wrist‐worn ActiGraph GT9X to derive the Pittsburgh Performance Fatigability Index (PPFI, higher scores = more severe fatigability) that quantifies percent decline in individual cadence‐versus‐time trajectory from their maximal cadence. Complex I&II‐supported maximal oxidative phosphorylation (max OXPHOS) and complex I&II‐supported electron transfer system (max ETS) were quantified ex vivo using high‐resolution respirometry in permeabilized fiber bundles from vastus lateralis muscle biopsies. Maximal adenosine triphosphate production (ATPmax) was assessed in vivo by 31P magnetic resonance spectroscopy. We conducted tobit regressions to examine associations of max OXPHOS, max ETS, and ATPmax with PPFI, adjusting for technician/site, demographic characteristics, and total activity count over 7‐day free‐living among older adults (N = 795, 70–94 years, 58% women) with complete PPFI scores and ≥1 energetics measure. Median PPFI score was 1.4% 25th–75th percentile: 0%–2.9%. After full adjustment, each 1 standard deviation lower max OXPHOS, max ETS, and ATPmax were associated with 0.55 (95% CI: 0.26–0.84), 0.39 (95% CI: 0.09–0.70), and 0.54 (95% CI: 0.27–0.81) higher PPFI score, respectively. Our findings suggested that therapeutics targeting muscle energetics may potentially mitigate fatigability and lessen susceptibility to disability among older adults.
Among 795 older adults from the Study of Muscle, Mobility and Aging, we found that each 1 standard deviation lower max OXPHOS, max ETS, and ATPmax were associated with 0.55 (95% CI: 0.26–0.84), 0.39 (95% CI: 0.09–0.70), and 0.54 (95% CI: 0.27–0.81) higher PPFI score, respectively. Our findings suggested that therapeutics targeting muscle energetics may potentially mitigate fatigability and lessen susceptibility to disability among older adults.
Abstract
Background
Low walking ability is highly prevalent with advancing age and predicts major health outcomes. Metabolomics may help to better characterize differences in walking ability among ...older adults, providing insight into potentially altered molecular processes underlying age-related decline in functioning. We sought to identify metabolites and metabolic pathways associated with high versus low walking ability among 120 participants ages 79–95 from the CHS All Stars study.
Methods
Using a nested case–control design, 60 randomly selected participants with low walking ability were matched one-to-one on age, gender, race, and fasting time with 60 participants with high walking ability. High versus low walking ability was defined as being in the best versus worst tertiles for both gait speed (≥0.9 vs <0.7 m/s) and the Walking Ability Index (7–9 vs 0–1). Using liquid chromatography-mass spectrometry, 569 metabolites were identified in overnight-fasting plasma.
Results
Ninety-six metabolites were associated with walking ability, where 24% were triacylglycerols. Triacylglycerols that were higher among those with high walking ability consisted mostly of polyunsaturated fatty acids, whereas triacylglycerols that were lower among those with high walking ability consisted mostly of saturated or monounsaturated fatty acids. Body composition partly explained associations between some metabolites and walking ability. Proline and arginine metabolism was a top pathway associated with walking ability.
Conclusion
These results may partly reflect pathways of modifiable risk factors, including excess dietary lipids and lack of physical activity, contributing to obesity and further alterations in metabolic pathways that lead to age-related decline in walking ability in this older adult cohort.
Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential ...genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30-110 years; 45% men).
Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center.
At baseline, 26.9% of individuals had "slow" gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of -0.02 ± 0.03 m/s per year (p < .0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24-0.32, p < .05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene.
Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.
When a 400‐m walk test with time constraint (in 15 minutes) is administered, analysis of the associated 400‐m gait speed can be challenging because some older adults are unable to complete the ...distance in time (noncompleters). A simplistic imputation method is to calculate the observed speeds of the noncompleters as the partially completed distance divided by the corresponding amount of elapsed time as an estimate of gait speed over the full 400‐m distance. This common practice has not been validated to the best of our knowledge. We propose a Bayesian multiple imputation (MI) method to impute the unobserved 400‐m gait speed for noncompleters. Briefly, MI is performed under the assumption that the unobserved 400‐m gait speed of noncompleters is left‐censored from a normal distribution. We illustrate the application of the Bayesian MI method using longitudinal data collected from the Lifestyle Interventions for Elders (LIFE) study. A simulation study was performed to assess the bias in estimation of the mean 400‐m gait speed using both methods. The results indicate that the simplistic imputation method tends to overestimate the population mean, whereas the Bayesian MI method yields minimal bias as the sample size increases.
OBJECTIVES Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. ...We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass ALM/ht(2)); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 +/- 2.3 years for mortality. SETTING Eight prospective observational cohort studies. PARTICIPANTS A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia.
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