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

## TL;DR

Muscle fiber disorganization, measured as entropy, is linked to reduced mobility and muscle function in older adults, suggesting entropy is a key factor in aging-related decline.

## Contribution

The study introduces a novel entropy framework to explain aging-related muscle dysfunction, independent of muscle mass.

## Key findings

- Higher muscle entropy correlates with slower walk speed and lower peak VO2 in older adults.
- Entropy is associated with decreased mitochondrial oxidative phosphorylation and muscle power.
- Entropy measures like HDI_M are strongly correlated with Shannon entropy of muscle fiber traits.

## Abstract

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.

Increased muscle entropy, measured by the homeostatic dysregulation index of muscle, reflects fiber disorganization. This accumulation of entropy independently contributes to declines in physical performance, muscle power, and mitochondrial energetics in older adults, establishing entropy as a key framework for skeletal muscle aging.