Molecular aspects of metformin’s anti-aging properties for muscle function and longevity in Drosophila melanogaster

Muscle aging, characterized by the progressive loss of muscle mass and function, presents a significant clinical challenge, contributing to sarcopenia and age-related frailty. Recent research highlights metformin, a widely used anti-diabetic drug, as a promising candidate for mitigating muscle aging by targeting conserved molecular pathways. This review explores metformin’s mechanisms in Drosophila melanogaster, emphasizing its activation of AMP-activated protein kinase (AMPK) and inhibition of the mechanistic target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (mTOR), pivotal regulators of cellular energy balance and proteostasis(definition). Metformin enhances autophagy(definition), reduces protein aggregation, and preserves muscle integrity by modulating autophagy-related genes, such as Atg1 and Atg8. Furthermore, the drug's suppression of ribosomal S6 kinase (S6K) and eukaryotic initiation factor 4E (eIF-4E) inhibits excessive protein synthesis, mitigating proteostatic stress. Studies in Drosophila reveal that metformin extends lifespan, reduces oxidative stress, and improves muscle function, offering insights into its translational potential for addressing sarcopenia. However, challenges remain in bridging the findings from Drosophila to humans due to species-specific differences and the need for long-term clinical studies. By elucidating the interplay of AMPK, mTOR, and autophagy pathways, this review underscores metformin’s therapeutic potential in age-related muscle decline, providing a molecular foundation for its application in geroprotective interventions. Future research should focus on optimizing dosing strategies, exploring synergistic therapies, and advancing biomarkers for muscle aging to fully harness metformin’s clinical utility in promoting healthy aging. • Metformin activates AMPK and inhibits mTOR to delay muscle aging. • Enhances autophagy and proteostasis, reducing protein aggregation. • Extends lifespan and improves muscle health in Drosophila melanogaster . • Offers therapeutic potential for sarcopenia and age-related muscle decline.