How are FTO and longevity related?

The relationship between FTO and longevity is indirect and primarily mediated through body fat. Risk variants in the FTO gene (e.g., rs9939609) are associated with higher BMI and obesity, which in turn increase the risk of cardiovascular disease, diabetes, and premature mortality. Some research suggests direct effects of FTO on cellular energy metabolism and mTOR signaling, which could theoretically influence lifespan. However, the evidence is mostly mechanistic and from animal models. Large GWAS on longevity (e.g., centenarian studies) typically do not find FTO variants as significant predictors. Therefore, the clinical link is weak: a DNA test for FTO can only indicate a genetic predisposition to obesity, not a direct measure of life expectancy. The predictive value is limited because lifestyle factors (diet, exercise) strongly override any genetic effect. Caution: FTO is not a 'longevity gene' in the strict sense.