Background: Longevity is considered the result of interactions between environmental and genetic factors.Aim: To investigate the possible association of body mass index and the frequencies of APOE, ACE, eNOS and FTO gene polymorphisms with longevity.Subjects and methods: In total, 1100 healthy volunteers aged 10-100 were recruited. Subjects were genotyped for APOE, ACE, eNOS and FTO gene polymorphisms. Data about height and weight were also collected. The sample was split into four age groups: 1-24, 25-49, 50-85 and 86-100 years.Results: Significant differences were found in BMI values between age groups. A significant decrease of the APOE4, eNOS 393 and FTO A and allele frequencies was observed in the 86-100 age group compared to the younger groups. For ACE gene, no significant differences were found in the allele frequencies between groups. A similar trend was also observed when the sample was subdivided into two main age groups: 1-85 and 86-100 years.Conclusion: This study provides evidence 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.