MITOCHONDRIA AND OXIDATIVE STRESS IN AGE-RELATED MUSCLE LOSS (SARCOPENIA)

Muscle wasting is due to an excessive activation of degradative pathways. It occurs in different pathologies such as cancer, AIDS, diabetes but inevitably it occurs in everybody’s life during aging. Sarcopenia is the degenerative loss of skeletal muscle mass and strength associated with aging. The ability to activate compensatory mechanisms in response to environmental stress and physiological changing is an important factor for survival and maintenance of cellular functions. A system that is often activated both in short and prolonged stress conditions is autophagy(definition). Autophagy is required to clear the cell from dysfunctional organelles and altered proteins and is reported to decline during ageing. This reduction might contribute to age-related organ dysfunction and, in general, to ageing. Here we report that specific autophagy inhibition in muscle has a major impact on this tissue that ultimately affect life span of animals. Inhibition of autophagy exacerbates the aging-related features of muscle such as atrophy, mitochondrial dysfunction(definition), oxidative stress and profound weakness. Mitochondrial dysfunction and oxidative stress directly affect acto-myosin interaction and force generation. These results demonstrate that aging-related muscle dysfunction is mainly caused by a failure of the autophagy system. It has been reported that lifestyle adaptations, such as caloric restriction(definition) and physical exercise are able to ameliorate several features during ageing process, moreover physical activity has been recently documented to play a fundamental physiological role in the regulation of autophagy in several tissues. Here we address also the role of autophagy during exercise. We reveal that autophagy is critical for the preservation of mitochondrial function during damaging muscle contraction. We establish that basal oxidative stress plays a crucial role in mitochondrial maintenance during normal physical activity. Therefore, autophagy is an adaptive response to exercise that ensures effective mitochondria-quality control during damaging physical activity.