What role does MTHFR play in longevity?

MTHFR's role in longevity is indirect and often overstated. The C677T variant (rs1801133) can reduce enzyme activity, leading to higher homocysteine levels if folate intake is low. Elevated homocysteine is a moderate risk factor for cardiovascular disease, which can shorten lifespan. However, large-scale studies show that the effect of common MTHFR variants on all-cause mortality is small and highly dependent on folate status. Direct longevity GWAS do not identify MTHFR as a major locus. Thus, the evidence is moderate: there is a plausible mechanism but limited clinical impact on individual lifespan. A DNA test alone cannot predict longevity; lifestyle, diet, and other genetic factors are more influential.