n-3 Polyunsaturated fatty acids improve sarcopenia by mitochondrial quality control

Accelerated global population aging has established sarcopenia as a critical public health burden, directly compromising health and independence in older adults. Converging evidence implicates mitochondrial dysfunction as pathogenic in sarcopenia, manifested through defective energy production, heightened oxidative stress, and compromised mitochondrial quality control (MQC). n-3 Polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), demonstrate significant potential to ameliorate mitochondrial impairments. Their mechanisms encompass: enhanced oxidative phosphorylation (OXPHOS) efficiency, activation of the NRF2-mediated antioxidant response, restoration of mitochondrial fission/fusion dynamics, and facilitation of PINK1/Parkin-dependent mitophagy. Critically, n-3 PUFAs activate the AMPK/SIRT1/PGC-1α axis to stimulate mitochondrial biogenesis, thereby augmenting mitochondrial content and supporting muscle regeneration. Notably, preclinical studies indicate superior efficacy of EPA over DHA in modulating MQC and preserving muscle function. This review synthesizes current mechanistic insights into n-3 PUFAs-mediated regulation of mitochondrial quality control and evaluates their therapeutic promise for attenuating age-related sarcopenia.