The Critical Role of Oxidative Stress in Sarcopenic Obesity

Figure 2

Oxidative stress in sarcopenic obesity. In older people, oxidative stress (Os) favors sarcopenia and obesity through mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and imbalance in muscle mass control. Mitochondrial dysfunction in sarcopenia is induced by Os due to mitochondrial DNA damage and impaired mechanisms for repairing DNA ability, impaired capacity to remove dysfunctional mitochondria, decreased mitochondrial quantity and quality, and impaired capacity to generate ATP to activate the apoptotic pathways. ER stress and Os are caused by an increase in adipose tissue, chronic inflammation, and insulin resistance, all of which are characteristics of obesity and aging. ER stress induces Os, favoring unfolded protein response (UPR) overactivation, imbalance in calcium homeostasis, increased protein aggregation, and decreased protein synthesis. Imbalance in muscle mass control occurs because Os increases the catabolic activity and decreases the anabolic pathway in muscle mass control. Os reduces protein synthesis due to the reduced activity in phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR). Os increases the activity of the ubiquitin-proteasome system (UPS) and activates muscle proteases such as caspases and calpains. Finally, due to Os, satellite cells’ quantity and regenerative function decline with age and obesity. Mitochondrial dysfunction, ER stress, and imbalance in the muscle mass control pathways induce lipotoxicity (Lptx), chronic inflammation, IR, and loss of muscle mass, affecting physical function and independence in sarcopenic obesity. Abbreviations: Os: oxidative stress; ER: endoplasmic reticulum; UPR: unfolded protein response; PI3K: phosphatidylinositol 3-kinase; Akt: serine-threonine kinase; mTOR: mammalian target of rapamycin; UPS: ubiquitin-proteasome system (UPS); Lptx: lipotoxicity.