The effects of glucagon and the target of rapamycin (TOR) on skeletal muscle protein synthesis and age-dependent sarcopenia in humans

Abstract

Background and aims: Human target of rapamycin (TOR) is a kinase that stimulates protein synthesis in the skeletal muscle in response to amino acids and physical activity.

Methods: A comprehensive literature search was conducted on the PubMed database from its inception up to May 2021 to retrieve information on the effects of TOR and glucagon on muscle function. Articles written in English regarding human subjects were included.

Results: l-leucine activates TOR to initiate protein synthesis in the skeletal muscle. Glucagon has a crucial role suppressing skeletal muscle protein synthesis by increasing l-leucine oxidation and the irreversible loss of this amino acid. Glucagon-induced l-leucine oxidation suppresses TOR and attenuates the ability of skeletal muscle to synthesize proteins. Conditions associated with increased glucagon secretion typically feature reduced ability to synthesize proteins in the skeletal muscle that may evolve into sarcopenia. Animal protein ingestion, unlike vegetable protein, stimulates glucagon secretion. High intake of animal protein increases l-leucine oxidation and promotes the use of amino acids as fuel. Sarcopenia and arterial stiffness characteristically occur together in conditions featuring insulin resistance, such as aging. Insulin resistance mediates the relationship between aging and sarcopenia and arterial stiffness. The loss of skeletal muscle fibers that characterizes sarcopenia is followed by collagen and lipid accumulation. Likewise, insulin resistance is associated with arterial stiffness and intima-media thickening due to adaptive accretion of collagen and lipids in the arterial wall.

Conclusions: Human TOR participates in the pathogenesis of sarcopenia and arterial stiffness, although its effects remain to be fully elucidated.

Keywords: Aging; Amino acids; Cardiovascular risk; Exercise; Glucagon; Insulin resistance; Protein synthesis; Sarcopenia; Sirolimus; Skeletal muscle; l-leucine.