How Do Skeletal Muscles Die? An Overview

Abstract

Clarifying the confusion regarding the term "muscle death" is of great importance, especially for clinicians. In response to various stimuli, skeletal muscle may undergo pathological changes, leading to muscle atrophy and consequently resulting in the loss of muscle strength and function. Depending on the stimulus, skeletal muscles can be induced to die through different mechanisms mainly via apoptosis, autophagy and necrosis. Muscle death may occur secondary to various physiological and pathological conditions such as aging, starvation, immobilization, denervation, inflammation, muscle diseases and cancer. This overview aims to elucidate the medical terminology and pathways used to describe muscle death, which are commonly confused. In addition, some of the common pathological conditions that lead to muscle death such as cachexia and sarcopenia of aging are dwelled on.

Sarcopenia in Older Adults

“…This chapter focuses on sarcopenia. Aged skeletal muscles can be induced to die through different mechanisms mainly via two systems, apoptosis or autophagy; both systems can be activated through different molecules such as free radicals, inflammatory molecules, hormones, and others [7].…”

Can Glucose-Insulin-Potassium Prevent Skeletal Muscle Ischemia-Reperfusion Injury?

“…Similar to cardiac muscle, skeletal muscle ischemia-reperfusion injury occurs through ischemic ATP depletion and reperfusionmediated ROS production [37]. ATP depletion destabilizes the electrochemical gradient of the sarcolemma, leading to increased intracellular proteolytic enzymes.…”

“…Excess ROS increases sarcolemma permeability, and similarly increases intracellular proteolytic enzymes [38]. These enzymes degrade the muscle cell, releasing large quantities of muscle breakdown products including myoglobin, CK, and lactate dehydrogenase that can be nephrotoxic [37]. Since GIK can mitigate these processes in cardiac muscle [19][20][21][22], it may have some utility in reducing skeletal muscle ischemiareperfusion injury.…”

Efficacy of Age-Specific High-Intensity Stretch-Shortening Contractions in Reversing Dynapenia, Sarcopenia, and Loss of Skeletal Muscle Quality

“…Indeed, it has been reported that, even in individuals that are otherwise considered "healthy", skeletal muscle mass has been shown to decrease~1% per year from its peak occurrence between the ages of 20-30 years old [44]. The loss of skeletal muscle mass is multi-factorial and many factors have been identified as contributors to this event; even though this is not an exhaustive list, a few of these factors are anabolic resistance [45][46][47], apoptosis [48,49], chronic inflammatory signaling associated with long-term, low-grade inflammation [50][51][52][53], and neuromuscular alterations such as motor unit loss that leads to skeletal muscle fiber denervation [45][46][47]. This latter event may be the most consequential, given that it could be thought of in terms of an explicit functional event: loss of motor units results in denervation and loss of skeletal muscle fibers, specifically the fastest skeletal muscle fibers, and finally loss of skeletal muscle function [54].…”