Human neuromuscular aging: Sex differences revealed at the myocellular level

Abstract

Age-related muscle loss (sarcopenia) is a major clinical problem affecting both men and women - accompanied by muscle weakness, dysfunction, disability, and impaired quality of life. Current definitions of sarcopenia do not fully encompass the age-related changes in skeletal muscle. We therefore examined the influence of aging and sex on elements of skeletal muscle health using a thorough histopathological analysis of myocellular aging and assessments of neuromuscular performance. Two-hundred and twenty-one untrained males and females were separated into four age cohorts [mean age 25 y (n = 47), 37 y (n = 79), 61 y (n = 51), and 72 y (n = 44)]. Total (-12%), leg (-17%), and arm (-21%) lean mass were lower in both 61 y and 72 y than in 25 y or 37 y (P < 0.05). Knee extensor strength (-34%) and power (-43%) were lower (P < 0.05) in the older two groups, and explosive sit-to-stand power was lower by 37 y (P < 0.05). At the histological/myocellular level, type IIx atrophy was noted by 37 y and type IIa atrophy by 61 y (P < 0.05). These effects were driven by females, noted by substantial and progressive type IIa and IIx atrophy across age. Aged female muscle displayed greater within-type myofiber size heterogeneity and marked type I myofiber grouping (~5-fold greater) compared to males. These findings suggest the predominant mechanisms leading to whole muscle atrophy differ between aging males and females: myofiber atrophy in females vs. myofiber loss in males. Future studies will be important to better understand the mechanisms underlying sex differences in myocellular aging and optimize exercise prescriptions and adjunctive treatments to mitigate or reverse age-related changes.

Keywords: Aging; Atrophy; Lean mass; Muscle power; Myofiber; Sarcopenia; Strength.

Fig. 1.

Lower total, leg, and arm lean body mass in older adults. Lean mass values for each individual are expressed relative to the mean of the 25 y group. †Main effect of age. ‡Main effect of sex; ¹P < 0.05 vs. 25 y; ²P < 0.05 vs. 37 y.

Fig. 2.

Differences in myofiber CSA across age groups. †Main effect of age. ‡Main effect of sex; *Within-group difference in males vs. females; ¹P < 0.05 vs. 25 y; ²P < 0.05 vs. 37 y.

Fig. 3.

Color histogram representing percentage of fibers of a given size within each group as a qualitative assessment of age-related atrophy and compensatory hypertrophy.