Autophagy in sarcopenic obesity: muscle-adipose crosstalk, metabolic regulation, and exercise-based interventions.

Sarcopenic obesity (SO) is a complex age-related phenotype characterized by the concurrent presence of reduced skeletal muscle mass, impaired muscle function, and excessive adiposity, which collectively contribute to metabolic dysfunction, physical decline, and increased mortality. Autophagy maintains cellular homeostasis by regulating protein turnover, mitochondrial quality control, lipid metabolism, and muscle-adipose crosstalk. However, aging, obesity, chronic low-grade inflammation, and insulin resistance may impair autophagic flux, thereby exacerbating muscle degeneration, ectopic lipid deposition, and metabolic imbalance. This narrative review synthesizes current evidence on exercise-modulated autophagic mechanisms in SO and examines how exercise modality, intensity, duration, and individual characteristics shape autophagic responses. Current evidence suggests that exercise may support autophagic homeostasis through multiple mechanisms, including AMPK/mTOR/ULK1, TFEB/FoxO, PGC-1α-related, sirtuin-dependent, and mitophagy-associated pathways. Different exercise modalities appear to confer distinct benefits: resistance exercise primarily promotes muscle anabolism and selective autophagy-related processes; aerobic exercise modulates mitophagy- and lipophagy-related processes; high-intensity interval training may induce rapid, although recovery-dependent, autophagy-related responses; combined exercise may provide a broader metabolic benefit by simultaneously reducing adiposity with muscle preservation. Based on available direct and indirect evidence, long-term, progressive, moderate-intensity resistance exercise combined with aerobic exercise may be a promising strategy for SO management. However, confirmation in SO-specific randomized controlled trials is warranted. Future studies integrating dynamic monitoring of autophagic flux, functional outcomes, and phenotype-stratified exercise prescriptions are needed to translate mechanistic insights into individualized interventions.