Aging Does Not Exacerbate Muscle Loss During Denervation and Lends Unique Muscle-Specific Atrophy Resistance With Akt Activation.

Jae-Sung You,Jie Chen

doi:10.3389/fphys.2021.779547

Abstract

Sarcopenia, or age-related skeletal muscle atrophy and weakness, imposes significant clinical and economic burdens on affected patients and societies. Neurological degeneration, such as motoneuron death, has been recognized as a key contributor to sarcopenia. However, little is known about how aged/sarcopenic muscle adapts to this denervation stress. Here, we show that mice at 27months of age exhibit clear signs of sarcopenia but no accelerated denervation-induced muscle atrophy when compared to 8-month-old mice. Surprisingly, aging lends unique atrophy resistance to tibialis anteria muscle, accompanied by an increase in the cascade of mammalian target of rapamycin complex 1 (mTORC1)-independent anabolic events involving Akt signaling, rRNA biogenesis, and protein synthesis during denervation. These results expand our understanding of age-dependent stress responses and may help develop better countermeasures to sarcopenia.

Highlights

Loss of skeletal muscle mass, or atrophy, can occur in a variety of conditions throughout life, including disuse, malnutrition, injury, diseases, and aging (You et al, 2015, 2018, 2021b)
In other muscles except for EDL, denervation reduced muscle mass and total protein content to a similar degree in adult and aged mice (Figures 1B–D). These results indicate that aged muscle is not more susceptible to denervation atrophy than younger muscle and rather exhibits atrophy resistance in a specific type of muscle
We found that the induction of Chrn subunits, muscle-specific kinase (Musk), Myog, and Histone Deacetylase 4 (HDAC4) by denervation surgery was generally repressed in the aged muscles (Figures 1E,F)

Summary

Introduction

Loss of skeletal muscle mass, or atrophy, can occur in a variety of conditions throughout life, including disuse, malnutrition, injury, diseases, and aging (You et al, 2015, 2018, 2021b). Age-related muscle atrophy and weakness (i.e., sarcopenia) in particular has rapidly become prevalent with increasing lifespan, and it is highly associated with loss of independence, an increased risk of morbidity and mortality, and a significant economic burden (Janssen et al, 2004; Larsson et al, 2019). In addition to its basal phenotypes, aged muscle exhibits distinct physiological and molecular responses to various stresses, such as overload, immobilization, and retraining/reloading after disuse (Hwee and Bodine, 2009; Suetta et al, 2009; Miller et al, 2019). Progressive perturbations in the motoneuron system (from pre-synaptic degeneration to motoneuron death or denervation) have been recognized

Methods

Results

Conclusion