Perturbations in genomic stability result in cancer, a reduced life span, and premature aging. MLH1 is a mismatch repair enzyme that acts to maintain genomic stability, and a loss of MLH1 increases cancer incidence and apoptosis resistance, which suggests a link between MLH1 and longevity. We found here that MLH1 is associated with longevity by comparing a centenarian group with a control group. Our data indicate a critical role for MLH1 in longevity.