Entropy of Muscle Fiber Histology Predicts Mobility in Older Adults: The Study of Muscle, Mobility, and Aging

Entropy may play an underappreciated role in human aging, such as in skeletal muscle functional declines. Histologically, muscle appears increasingly disorganized with aging, with greater fiber size variability and fiber-type grouping. We tested the hypothesis that entropy is associated with reduced physical performance and muscle function, independent of muscle mass. We quantified a homeostatic dysregulation index of muscle (HDI_M) as a proxy for entropy of muscle fiber disorganization based on cross-sectional images of vastus lateralis biopsies from 299 adults age 70 or older. HDI_M was derived from three traits: fiber area diversity, fiber-type heterogeneity, and the mean of the shortest path lengths through adjacent fiber networks. HDI_M derived from muscle fibers was highly correlated with Shannon entropy, a different measure of entropy of muscle fiber traits. Higher HDI_M derived from participants was associated with slower 400-m walk speed, lower peak VO₂, muscle power, and decreased maximum rate of oxidative phosphorylation by mitochondria in muscle. These findings suggest that muscle fibers accumulate entropy with aging which contributes to decline in physical performance, muscle power, and mitochondrial energetics, advancing the entropy framework in aging research.