Food-derived bioactive compounds targeting mitophagy: Emerging nutritional strategies against sarcopenia

Background

Sarcopenia, the age-related loss of skeletal muscle mass and strength, has emerged as a major global health challenge due to its impact on mobility, independence, and mortality in aging populations. Mitochondrial dysfunction—particularly impaired mitophagy—plays a central role in muscle aging and degeneration. Recent studies suggest that specific dietary compounds can modulate mitophagy and potentially mitigate sarcopenia progression through nutritional strategies.

Scope and approach

This review categorizes food-derived bioactives that have demonstrated or proposed potential to modulate mitophagy and thereby ameliorate sarcopenia into five major classes, including polyphenols, polysaccharides, terpenoids, polyunsaturated fatty acids, and other emerging modulators. Mechanistic insights are critically examined across cellular, animal, and human studies. We also discuss key translational opportunities and barriers, including biomarker development, personalization, synergistic design, formulation strategies, and regulatory considerations.

Key findings and conclusions

While many compounds demonstrate mitophagy-modulating effects in preclinical studies, clinical translation is still limited. Urolithin A currently provides the most consistent human evidence, improving mitophagy markers and functional outcomes in randomized trials, thereby offering proof-of-concept for this nutritional strategy. However, broader translation requires standardized biomarkers, integration of omics-based stratification, optimized delivery systems, and alignment with regulatory frameworks. A coordinated, multi-level approach that links molecular efficacy with clinical outcomes and practical applications will be essential for establishing mitophagy-targeted nutrition as a credible strategy for sarcopenia prevention and healthy aging.