Metformin at the convergence of aging and longevity

Metformin is a biguanide and first line drug for type 2 diabetes (T2D) mellitus that is being recognized as a geroprotective agent capable of influencing important hallmarks of aging. Apart from its primary role in lowering blood glucose levels, metformin has been shown to have several effects at the molecular level. It acts by activating the AMPK, which leads to a cascade of downstream events such as the inhibition of mTOR, increased mitochondrial biogenesis, and autophagy, as well as epigenetic modifications. Current findings also showed its capacity to alter the gut microbiota by increasing short-chain fatty acid producing bacteria, indicating the involvement of other systemic pathways that aid in lowering inflammation, increasing metabolic fitness, and keeping epigenetic stability. The Targeting Ageing with Metformin (TAME), a landmark trial which seeks to evaluate metformin's ability to slow down several age-associated diseases, could lead to a paradigm shift in the clinical approach to aging. This article looks at metformin's various effects on aging and longevity by consolidating findings from cellular, molecular, and organismal levels. It also calls for more studies and trials on metformin and aging.