Chronic Inflammation and Mitochondrial Dysfunction Interact in the Production of Sarcopenia
Sarcopenia is the name given to the later stages of the characteristic loss of muscle mass and strength that occurs in every individual with aging, eventually leading to weakness and the state of frailty. There are many possible contributing mechanisms, and those mechanisms interact with one another. One important cause is loss of muscle stem cell activity, but this may be driven by any number of other aspects of aging. Another important contribution is dysfunction of neuromuscular junctions, as loss of innervation tends to have a negative impact on tissue maintenance. This again may be driven by any number of causative mechanisms of aging. Further, stem cell dysfunction may interact with neuromuscular junction dysfunction. The situation is complex.
Of the hallmarks of aging, both (a) loss of mitochondrial function and (b) sustained, unresolved inflammation receive a great deal of attention from the scientific community. Researchers here outline some of the interactions that take place between a state of chronic inflammatory signaling and a state of mitochondrial dysfunction that cause both sides to make the other worse. In turn, both chronic inflammation and mitochondrial dysfunction separately contribute to aspects of sarcopenia, harming the function of cells and structures that are necessary to the processes of muscle tissue maintenance.
Sarcopenia, characterized by the insidious reduction of skeletal muscle mass and strength, detrimentally affects the quality of life in elderly cohorts. Present therapeutic strategies are confined to physiotherapeutic interventions, signaling a critical need for elucidation of the etiological underpinnings to facilitate the development of innovative pharmacotherapies. Recent scientific inquiries have associated mitochondrial dysfunction and inflammation with the etiology of sarcopenia. Mitochondria are integral to numerous fundamental cellular processes within muscle tissue, including but not limited to apoptosis, autophagy, signaling via reactive oxygen species, and the maintenance of protein equilibrium. Deviations in mitochondrial dynamics, coupled with compromised oxidative capabilities, autophagic processes, and protein equilibrium, result in disturbances to muscular architecture and functionality.
Mitochondrial dysfunction is particularly detrimental as it diminishes oxidative phosphorylation, escalates apoptotic activity, and hinders calcium homeostasis within muscle cells. Additionally, deleterious feedback loops of deteriorated respiration, exacerbated oxidative injury, and diminished quality control mechanisms precipitate the acceleration of muscular senescence. Notably, mitochondria exhibiting deficient energetic metabolism are pivotal in precipitating the shift from normative muscle aging to a pathogenic state.
This analytical review meticulously examines the complex interplay between mitochondrial dysfunction, persistent inflammation, and the pathogenesis of sarcopenia. It underscores the imperative to alleviate inflammation and amend mitochondrial anomalies within geriatric populations as a strategy to forestall and manage sarcopenia. An initial overview provides a succinct exposition of sarcopenia and its clinical repercussions. The discourse then progresses to an examination of the direct correlation between mitochondrial dysfunction and the genesis of sarcopenia. Concomitantly, it accentuates potential synergistic effects between inflammatory responses and mitochondrial insufficiencies during the aging of skeletal muscle, thereby casting light upon emergent therapeutic objectives.