Abstract

The role that mtDNA heteroplasmy plays in healthy aging, familial longevity and the heritability patterns of low levels heteroplasmy in the elderly are largely unknown. We analyzed the low levels of mtDNA heteroplasmy in blood in a cohort of centenarians, their offspring and a group of offspring of non long-lived parents, characterized by a less favorable health phenotype. The aims of this study are to: (i) investigate the transmission of low level heteroplasmies in the elderly; (ii) explore the association of heteroplasmy with age and longevity and (iii) investigate heteroplasmy patterns in these three groups. We sequenced a 853 bp mtDNA fragment in 88 individuals to an average coverage of 49334-fold, using quality control filtering and triplicate PCR analysis to reduce any methodological bias, and we detected 119 heteroplasmic positions with a minor allele frequency ≥ 0.2%. The results indicate that low-level heteroplasmies are transmitted and maintained within families until extreme age. We did not find any heteroplasmic variant associated with longevity and healthy aging but we identified an unique heteroplasmy profile for each family, based on total level and positions. This familial profile suggests that heteroplasmy may contribute to familial longevity.