Mammalian Target of Rapamycin (mTOR) Signaling at the Crossroad of Muscle Fiber Fate in Sarcopenia

Abstract

The mammalian target of rapamycin (mTOR) is a major regulator of skeletal myocyte viability. The signaling pathways triggered by mTOR vary according to the type of endogenous and exogenous factors (e.g., redox balance, nutrient availability, physical activity) as well as organismal age. Here, we provide an overview of mTOR signaling in skeletal muscle, with a special focus on the role played by mTOR in the development of sarcopenia. Intervention strategies targeting mTOR in sarcopenia (e.g., supplementation of plant extracts, hormones, inorganic ions, calorie restriction, and exercise) have also been discussed.

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

“…Many downstream pathways and factors relating to muscle regeneration may be regulated and activated by mitochondria, including the mammalian target of rapamycin complex 1 (mTORC1), Kelch-like ECH-associated protein 1 (KEAP1), and NF-E2-related factor 2 (NRF2) ( Rai and Dey, 2020 ). The mammalian target of rapamycin (mTOR) has been proven to be the key regulator of muscle regeneration and to regulate bone metabolism by stimulating protein synthesis and inhibiting proteolysis ( Sirago et al, 2022 ). Inflammaging, a chronic inflammatory phenomenon occurring in older individuals and characterized by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokine levels, was also a cause of many geriatric syndromes, including sarcopenia ( Bencivenga et al, 2022 ).…”

The frequency of sarcopenia has increased in patients with glomerulonephritis

“…Recent studies emphasize that calcineurin and mTOR inhibitors, which are other immunosuppressive agents used in patients, also cause muscle atrophy since it disrupts protein metabolism. The mTOR pathway, which has an anabolic effect on muscle protein metabolism and skeletal muscles, plays an essential role in cell growth 27 . Yoshino et al showed that when Omega‐3 polyunsaturated fatty acids were added to the diet, the inhibition of the mTOR pathway decreased, which had positive results in skeletal muscle production 28 .…”

“…The mTOR pathway, which has an anabolic effect on muscle protein metabolism and skeletal muscles, plays an essential role in cell growth. 27 Yoshino et al showed that when Omega-3 polyunsaturated fatty acids were added to the diet, the inhibition of the mTOR pathway decreased, which had positive results in skeletal muscle production. 28 Calcineurin inhibitors (e.g., cyclosporine, tacrolimus, etc.)…”

Mitochondrial Quantity and Quality in Age-Related Sarcopenia

“…mTOR is another major regulator of myocyte homeostasis [13]. Hyperactivation of mTOR during aging has a negative impact on muscle protein synthesis and favors muscle loss [87].…”

“…Additional systems have been implicated in the regulation of muscle plasticity and trophism such as the tightly modulated and complex interplay between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism [13].…”