Muscle metabolism and atrophy: let's talk about sex

Abstract

Skeletal muscle health is a strong predictor of overall health and longevity. Pathologies affecting skeletal muscle such as cancer cachexia, intensive care unit treatment, muscular dystrophies, and others are associated with decreased quality of life and increased mortality. Recent research has begun to determine that these muscular pathologies appear to present and develop differently between males and females. However, to our knowledge, there has yet to be a comprehensive review on musculoskeletal differences between males and females and how these differences may contribute to sex differences in muscle pathologies. Herein, we present a review of the current literature on muscle phenotype and physiology between males and females and how these differences may contribute to differential responses to atrophic stimuli. In general, females appear to be more susceptible to disuse induced muscle wasting, yet protected from inflammation induced (such as cancer cachexia) muscle wasting compared to males. These differences may be due in part to differences in muscle protein turnover, satellite cell content and proliferation, hormonal interactions, and mitochondrial differences between males and females. However, more works specifically examining muscle pathologies in females are necessary to more fully understand the inherent sex-based differences in muscle pathologies between the sexes and how they may correspond to different clinical treatments.

Keywords: Cancer cachexia; Disuse; Hormones; Mitochondria; Muscle atrophy; Sex differences.

Fig. 1

Summary of current literature of sex differences and similarities of muscle phenotype in males and females

Fig. 2

Summary of the current literature of classical sex hormones and their influence on muscle size.

Fig. 3

Summary of current data on mitochondrial differences between males and females as well as mitochondrial interventions for disuse atrophy