Evidence points to increased autophagy as an important factor in many of the interventions that slow aging to extend life in short-lived laboratory species such as flies, worms, and mice. Autophagy is a collection of cellular maintenance processes responsible for clearing out excess and damaged structures in the cell, transporting them to a lysosome for disassembly. In principle, fewer damaged components leads to improved function across the board, and thus a greater resilience to the damage and dysfunction of aging.
Mild stresses placed on cells provoke greater autophagy. These include transient lack of nutrients, heat, cold, and excess oxidative molecules produced by mitochondria during periods of high energy demand, such as during exercise. The biochemistry of autophagy in longer-lived mammalian species such as our own in response to these interventions is very similar, at least where the data exists to make the comparison, such as for exercise and calorie restriction. Nonetheless, life span in longer-lived species changes little in response to greater autophagy: a calorie restricted mouse can live as much as 40% longer, but that certainly isn't true for humans.
Exercise-driven cellular autophagy: A bridge to systematic wellness
Among various interventions, physical exercise is recognized as a structured, intentional form of physical activity that enhances physical fitness, prevents diseases, and aids in recovery. Despite extensive research on its systemic benefits, the molecular mechanisms underlying exercise-induced health improvements remain incompletely understood, particularly regarding its impact on cellular processes across organ systems. One such cellular process is autophagy, a conserved metabolic pathway that maintains cellular homeostasis by degrading and recycling intracellular components. Autophagy is critical for cellular survival, development, and differentiation, as well as for mitigating diseases and maintaining health. Dysregulated autophagy is implicated in various pathological conditions, including neurodegenerative diseases, cancer, and metabolic disorders, highlighting its therapeutic potential.
Autophagy is indispensable for maintaining cellular health and is often impaired in systemic diseases. Interestingly, physical exercise-a macroscopic, non-pharmacological intervention-has been shown to activate autophagy, indicating a potentially critical link between these two processes. While numerous studies have independently explored the benefits of exercise and the mechanisms of autophagy, a comprehensive understanding of how exercise-induced autophagy contributes to systemic health and disease recovery is still lacking. Specifically, the molecular basis by which exercise modulates autophagic flux across different tissues and its implications for treating systemic diseases remains an area of limited clarity.
This review aims to address this knowledge gap by synthesizing current evidence on the role of exercise-induced autophagy in promoting health and mitigating disease. We will focus on the molecular mechanisms by which exercise regulates autophagy, the tissue-specific impacts of this regulation, and the potential therapeutic applications of targeting autophagy activation through exercise.
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