How are COMT and longevity related?

The relationship between COMT (catechol-O-methyltransferase) and longevity is complex and not firmly established. COMT degrades catecholamines like dopamine and estrogens. The common rs4680 (Val158Met) polymorphism alters enzyme activity: the Val variant is high-activity, the Met variant low-activity. Some studies suggest the Met variant may be associated with better cognitive aging but also with increased stress reactivity. Other research links COMT to estrogen metabolism, potentially influencing female lifespan. However, effect sizes are small, population-specific, and confounded by many other genetic and environmental factors. Evidence comes mainly from candidate gene studies and GWAS, not from interventional trials. A direct causal role in determining maximum lifespan is not proven. For individual longevity prediction, COMT alone is insufficient. Consumer DNA tests marketing COMT as a 'longevity gene' should be viewed as speculative and primarily marketing-driven.