Aging-associated Aberrant Mitochondrial Redox Signaling, Physical Activity, and Sarcopenia.

Abstract

Aging-related alteration of mitochondrial morphology, impairment in metabolic capacity, bioenergetics, and biogenesis are closely associated with loss of muscle mass and function. Mitochondrial Reactive Oxygen Species (ROS) stimulate muscular redox signaling mechanisms. Bioenergetic integrity of mitochondria and redox signaling dynamics deteriorates in aged skeletal muscle. Mitochondrial bioenergetic impairment leads to excessive ROS levels and induces the generation of defective mitochondria. Higher ROS levels may induce senescence or apoptosis. It is not a resolved issue that mitochondrial dysfunction is either the sole reason or a consequence of muscle loss (or both). However, Increasing evidence emphasizes that dysregulated mitochondrial redox signaling has a central role in age-related muscle loss. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates redox signaling pathways with the expression of antioxidant genes. As the aberrant redox signaling mechanisms in aging skeletal muscle become clearer, new natural and synthetic Nrf2-modulating substances and integrated daily physical activity alternatives are coming into view for preventing muscle loss in the elderly. A comprehensive understanding of the relationship between redox signaling pathways and age-related sarcopenia can help us to prevent sarcopenia and its frailty effects with an optimized exercise program as an innovative non-pharmacological therapeutic approach. A further aspect is necessary to consider both individualized physical training options and alternative Nrf2 signaling modulators. Ameliorating the redox signaling with physical activity and pharmacological interventions may help to prevent sarcopenia and its frailty effects.