¹Department of Cell Biology, University of Calabria, Rende, Italy

²Department of Internal Medicine, University of Genova, Genova, Italy

³Department of Experimental Pathology, University of Bologna, Bologna, Italy

⁴National Institute for Aging Research (INRCA), Ancona, Italy

Correspondence to: G De Benedictis, Department of Cell Biology, University of Calabria. 87030 Rende, Italy. Tel. +39 0984 492932; Fax +39 0984 492911; E-mail: g.debenedictis@unical.it

Previous studies have shown that mitochondrial DNA (mtDNA) haplogroup J is significantly over-represented in healthy centenarians with respect to younger controls, thus suggesting that this haplogroup predisposes to successful aging and longevity. On the other hand, the same haplogroup is reported to have elevated frequency in some complex diseases. To verify if centenarians clustered in a particular lineage within J we have sequenced the D-loop region from 18 centenarians and 18 younger controls, previously characterized to be J. Then the entire mtDNA molecule was sequenced in a sub-sample of nine centenarians to find possible functional mutations associated with haplogroup J in successful aging. No clustering of the J haplogroup mtDNA from centenarians was observed. In addition, most of the mutations found are known as disease-associated mutations. The general picture that emerges from the study is that the J haplogroup of centenarians is surprisingly similar to that found in complex diseases, as well as in Leber Hereditary Optic Neuropathy. This finding implies that the same mutations could predispose to disease or longevity, probably according to individual-specific genetic backgrounds and stochastic events. This data reveals another paradox of centenarians and confirms the complexity of the longevity trait. European Journal of Human Genetics (2001) 9, 701-707.

aging; longevity; mitochondrial DNA