Backgroundlongevity is considered the result of interactions between environmental and genetic factors.\n\nAimwe investigated the possible association of body mass index and the frequencies of APOE, ACE, eNOS, and FTO gene polymorphisms with longevity.\n\nSubjects and Method1,100 healthy volunteers aged 10-100 were recruited. We genotyped subjects for APOE, ACE, eNOS, and FTO gene polymorphisms. Data about height and weight were also collected. The sample was split in four age groups: 1-24, 25-49, 50-85 and 86-100.\n\nResultssignificant differences were found in BMI values between age groups, with exception of 1-24 with respect to 86-100. A significant decrease of the APO E4, eNOS 393 and FTO A and allele frequencies was observed in the 86-100 age group with respect to younger groups. For ACE gene, no significant differences were found in the allele frequencies between groups. A similar trend was also observed subdividing the sample in two main age groups: 1-85 and 86-100.\n\nConclusionthis study provides evidences for a role of APOE, eNOS, and FTO gene polymorphisms in longevity. It has been estimated that the number of centenarians worldwide will double each decade until 2100, making population data about gene polymorphisms relevant for further studies about longevity.