# Metformin for Longevity and Sarcopenia: A Therapeutic Paradox in Aging

## TL;DR

Metformin may help protect against aging-related muscle loss in some people but could hinder muscle growth in others, highlighting the need for personalized approaches.

## Contribution

The paper identifies a therapeutic paradox in metformin's effects on muscle aging, suggesting context-dependent outcomes in different populations.

## Key findings

- Metformin is linked to reduced sarcopenia in insulin-resistant older adults through metabolic and anti-inflammatory effects.
- In healthy older adults, metformin may suppress muscle hypertrophy by activating AMPK and inhibiting mTORC1.
- The drug's effects highlight a paradoxical role in aging, requiring precision strategies for optimal geropharmacology.

## Abstract

Metformin is a first-line oral antidiabetic agent that has attracted increasing interest as a potential geroprotective therapy due to its ability to improve metabolic homeostasis, reduce oxidative stress, and attenuate chronic inflammation. However, its role in skeletal muscle aging and sarcopenia remains controversial. Observational and epidemiological studies suggest that metformin use is associated with a lower prevalence of sarcopenia, particularly in metabolically compromised or insulin-resistant older populations, where improvements in systemic metabolism and inflammatory burden may indirectly support muscle quality and function. In contrast, randomized interventional trials in metabolically healthy older adults indicate that metformin can blunt resistance exercise–induced muscle hypertrophy and protein synthesis, likely through sustained activation of AMP-activated protein kinase (AMPK) and consequent suppression of mammalian target of rapamycin complex 1 (mTORC1) signaling. This perspective argues that these apparently opposing outcomes reflect a con-text-dependent therapeutic paradox rather than inconsistent evidence. Metformin may provide metabolic protection in frail, insulin-resistant individuals, yet limit anabolic adaptations in physically active older adults. These findings emphasize the necessity for precision geropharmacological strategies to balance metabolic longevity with preservation of musculoskeletal health in aging populations.