Exercise and mitochondrial mechanisms in patients with sarcopenia

Abstract

Sarcopenia is a severe loss of muscle mass and functional decline during aging that can lead to reduced quality of life, limited patient independence, and increased risk of falls. The causes of sarcopenia include inactivity, oxidant production, reduction of antioxidant defense, disruption of mitochondrial activity, disruption of mitophagy, and change in mitochondrial biogenesis. There is evidence that mitochondrial dysfunction is an important cause of sarcopenia. Oxidative stress and reduction of antioxidant defenses in mitochondria form a vicious cycle that leads to the intensification of mitochondrial separation, suppression of mitochondrial fusion/fission, inhibition of electron transport chain, reduction of ATP production, an increase of mitochondrial DNA damage, and mitochondrial biogenesis disorder. On the other hand, exercise adds to the healthy mitochondrial network by increasing markers of mitochondrial fusion and fission, and transforms defective mitochondria into efficient mitochondria. Sarcopenia also leads to a decrease in mitochondrial dynamics, mitophagy markers, and mitochondrial network efficiency by increasing the level of ROS and apoptosis. In contrast, exercise increases mitochondrial biogenesis by activating genes affected by PGC1-ɑ (such as CaMK, AMPK, MAPKs) and altering cellular calcium, ATP-AMP ratio, and cellular stress. Activation of PGC1-ɑ also regulates transcription factors (such as TFAM, MEFs, and NRFs) and leads to the formation of new mitochondrial networks. Hence, moderate-intensity exercise can be used as a non-invasive treatment for sarcopenia by activating pathways that regulate the mitochondrial network in skeletal muscle.

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

“…In accordance with the rapid development of muscle weakness and the degradation of muscle mass due to critical illness, the decrease in mitochondrial content can be observed within several days after ICU admission [ 83 ]. Besides the inflammatory and metabolic challenges, critical illness is accompanied by physical inactivity, a factor which, by itself, is strongly associated with mitochondrial alterations [ 105 ].…”

High‐intensity interval training in the form of isometric contraction improves fatigue resistance in dystrophin‐deficient muscle

“…Mitochondrial health is improved by exercise training through both mitochondrial biogenesis and removal of dysfunctional mitochondria via mitophagy (Alizadeh Pahlavani et al., 2022; Sanchez et al., 2014). The AMP‐activated protein kinase (AMPK), a major sensor of cellular energy status, has been highly implicated in skeletal muscle adaptation in response to exercise training (Egan & Zierath, 2013).…”

Mitochondria Transplantation from Stem Cells for Mitigating Sarcopenia

“…Exercise can also improve the function of mitochondria by increasing markers of mitochondrial fusion, fission, and biogenesis [14]. However, there are limitations to exercise-based treatment, such as limited benefits for inactive patients, the absence of standardized approaches, and poor patient compliance.…”