Metformin

Evidence in longevity: the Bannister observational study (2014, UK GP database, 180,000 patients) showed that diabetics treated with metformin lived on average longer than non-diabetics without metformin. This motivated the TAME trial (Targeting Aging with Metformin) led by Nir Barzilai (Albert Einstein), designed to evaluate whether metformin delays the onset of multiple age-related chronic diseases in non-diabetic people aged 65-79.

Documented anti-ageing mechanisms: AMPK activation → mTOR inhibition → autophagy, IGF-1 reduction, modulation of gut microbiota (increased Akkermansia muciniphila), anti-inflammatory effect (reduces NF-κB), reduction of cancer incidence (15-20% in observational studies), epigenetic improvement (reduction of biological age measured by GrimAge in some studies).

Recent controversies: the MASTERS study (2019) suggested that metformin could attenuate strength-training adaptations in older adults — implying cycling metformin around heavy training or using lower doses.

Usual dosing: 500-2000 mg/day, ideally the XR (extended release) formulation for better gastrointestinal tolerance. B12 supplementation is mandatory (metformin interferes with its intestinal absorption). In Spain it requires medical prescription; off-label use in non-diabetics requires individualised prescription under medical judgement.