Metformin and the molecular pathways of aging: Searching for the modern elixir of life.

Abstract

Metformin, a well-established antidiabetic drug, has recently gained attention in geroscience for its potential to modulate key aging-related pathways. This review aims to summarize current knowledge regarding metformin's mechanisms of action beyond glycemic control, with emphasis on its influence on molecular hallmarks of aging and its potential as a geroprotective agent. A comprehensive literature review was conducted using scientific databases to synthesize findings from in vitro, in vivo, and clinical studies investigating the effects of metformin on aging-related processes. Particular attention was given to studies elucidating the drug's biochemical pathways and its role in age-associated diseases. Evidence indicates that metformin affects several hallmarks of aging, including mitochondrial dysfunction, oxidative stress, chronic inflammation, and cellular senescence. Mechanistically, activation of adenosine monophosphate-activated protein kinase (AMPK) and inhibition of mitochondrial Complex I are central to its systemic actions. These effects contribute to improved metabolic regulation, reduced production of reactive oxygen species, and enhanced autophagy. Additionally, metformin has shown protective effects in age-related disorders such as cardiovascular disease, neurodegeneration, and cancer. Its long-standing clinical use, low toxicity, and cost-effectiveness further support its relevance in aging research.