Sex differences in the association between skeletal muscle energetics and perceived physical fatigability: the Study of Muscle, Mobility and Aging (SOMMA).

Gay, Coen, Harrison, Garcia, Qiao, Goodpaster, Forman, Toledo, Distefano, Kramer, Ramos, Molina, Nicklas, Cummings, Cawthon, Hepple, Newman, Glynn. Sex differences in the association between skeletal muscle energetics and perceived physical fatigability: the Study of Muscle, Mobility and Aging (SOMMA). GeroScience. 2025 Apr 1; 47(2):1999-2013, DOI: 10.1007/s11357-024-01373-z.

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Abstract:

Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher = greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher = greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N = 873) were 76.3 ± 5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo) were associated with lower perceived physical fatigability, all p < 0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE Fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS ≥ 25, RPE Fatigability ≥ 12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p < 0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the ex vivo measures (p < 0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.