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.

Partial Weight-Bearing in Female Rats: Proof of Concept in a Martian-Gravity Analog

“…Like other physiological systems (Hefferan et al, 2003;Glenmark et al, 2004;Foley et al, 2005), muscle displays sexbased differences in both phenotype and mechanism during states of enforced disuse (Ploutz-Snyder et al, 2014;Rosa-Caldwell and Greene, 2019). Since few studies have aimed at investigating male and female rats concomitantly, and because of the various models and durations employed, a consensus has yet to be reached regarding the effect of sex differences in muscle deconditioning.…”

“…In Wistar rats, it has been shown that males have myofibers with greater cross-sectional area than females (Deschenes et al, 2018), and that they display a greater proportion of type 1 myofibers (Simard et al, 1987;Nakano et al, 1995;Novák et al, 2010), especially in the soleus, one of the muscles that atrophies most rapidly in response to mechanical unloading. Since unloadinginduced atrophy primarily affects oxidative (type 1) myofibers (Rosa-Caldwell and Greene, 2019), and leads to a fiber switch from type 1 to type 2 (Mortreux et al, 2019b), it is likely that partial mechanical unloading will yield different results in females compared to male rats, and thus demand for specific mitigating strategies.…”

Risk Factors for Muscle Loss in Hemodialysis Patients with High Comorbidity

“…There are clear sex differences in skeletal muscle kinetics and fiber-type composition [41]. In addition, there are several theoretical explanations for sex differences in muscle wasting, including the anabolic effects of testosterone, and the anti-inflammatory effects of estrogen [42,43]. Testosterone deficiency is especially common in male dialysis patients with low muscle mass [44] and this may have contributed to the greater LTM loss over time.…”

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

“…However, the astronauts’ population remains very heterogeneous in sex, age, mission duration, and mission protocols. More so, it is clear males and females have different musculoskeletal [ 117 , 118 , 119 ], cardiovascular [ 120 , 121 ] and overall physiology that may contribute to differential responses to micro- and partial gravity. As such, it is of the utmost importance to study adult female animals, in order to understand the sex-based differences in the adaptations to partial gravity, and thus develop the best countermeasures for both males and females.…”