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

A homeostatic dysregulation index of muscle (HDIM) was developed as a proxy for entropy of muscle fiber disorganization from vastus lateralis biopsies.

• HDIM was derived from cross-sectional images of vastus lateralis biopsies from 299 adults aged 70 or older.
• HDIM was constructed from three traits: fiber area diversity, fiber-type heterogeneity, and the mean of the shortest path lengths through adjacent fiber networks.
• HDIM was highly correlated with Shannon entropy, a different measure of entropy of muscle fiber traits.

Higher HDIM was associated with slower 400-meter walk speed in older adults.

• The association was independent of muscle mass.
• Participants were age 70 or older (n=299) from the Study of Muscle, Mobility, and Aging.

Higher HDIM was associated with lower peak VO2 in older adults.

• The association was observed independent of muscle mass.
• Peak VO2 reflects cardiorespiratory fitness and oxidative capacity.

Higher HDIM was associated with lower muscle power in older adults.

• The association was independent of muscle mass.
• This finding supports the role of muscle fiber disorganization in functional muscle decline.

Higher HDIM was associated with decreased maximum rate of oxidative phosphorylation by mitochondria in muscle.

• This finding links muscle fiber entropy to mitochondrial energetics.
• The association was independent of muscle mass.
• The result advances the entropy framework by connecting histological disorganization to mitochondrial function.

Muscle appears increasingly histologically disorganized with aging, characterized by greater fiber size variability and fiber-type grouping.

• Fiber-type grouping and fiber size variability are established histological features of aged skeletal muscle.
• These features served as the basis for quantifying entropy via HDIM in this study.
• The authors frame this disorganization within an entropy framework of aging.