Skeletal Muscle Energetics And Perceived Physical Fatigability Severity: The Study Of Muscle, Mobility And Aging

Greater perceived physical fatigability in older adults is associated with poor physical function, mobility decline, and mortality. Prior work has found that maximal ATP production (ATPmax) in skeletal muscle was related to higher perceived exertion (ie, fatigability). PURPOSE: Examine association between in vivo and ex vivo skeletal muscle energetics and perceived physical fatigability severity in the Study of Muscle, Mobility and Aging (SOMMA). METHODS: ATPmax was assessed by 31P magnetic resonance spectroscopy after an acute bout of knee extensor contractions. Ex vivo measures of maximal complex I&II supported oxidative phosphorylation (max OXPHOS) and maximal complex I&II and fatty acid supported oxidative phosphorylation (max FAO OXPHOS) were quantified in permeabilized fiber bundles by high-resolution respirometry. Rating of perceived exertion fatigability (RPE Fatigability) was measured using Borg Scale (range, 6-20) at end of a slow 5-minute treadmill walk (0.67 m/s, 0% grade); participants were classified into 4 strata: 6-7 least severe (reference, n = 360), 8-9 mild (n = 257), 10-11 moderate (n = 103), ≥12 most severe (n = 58). Individual multinomial logistic regression models examined associations between muscle energetics and RPE fatigability severity adjusted for age, sex, site/technician, BMI, total activity count, and multimorbidity. RESULTS: SOMMA participants (n = 778 with RPE Fatigability and ≥ 1 energetics measure) were 76.3 ± 5.0 years, 59.2% women, 85.3% White. One standard deviation (1SD) higher ATPmax (0.15 mM/sec) was associated with 50% lower odds of being in most vs least severe fatigability strata (OR = 0.50, 95% CI 0.32-0.79, p = .003. 1SD higher max OXPHOS (18.4 pmol/(s*mg)) was associated with 43% lower odds of being in most vs least severe fatigability strata (OR = 0.57, 95% CI 0.35-0.92, p = .01). 1SD higher max FAO OXPHOS (17.9 pmol/(s*mg)) was associated with 47% lower odds of being in most vs least severe fatigability strata (OR = 0.53, 95% CI 0.30-0.93, p = .03). CONCLUSION: Better mitochondrial energetics was linked to lower odds of fatigability severity during walking. Data imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging. Funding: NIH R01 AG059416, P30 AG024827, P30 AG021332, UL1 TR001420. NIH R01 AG059416, P30 AG024827, P30 AG021332, UL1 TR001420