Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians

Previous studies have shown that mitochondrial DNA (mtDNA) haplogroup J is significantly over-represented in healthy centenarians with respect to youn ger controls, thus suggesting that this haplogroup predisposes to successfu l aging and longevity. On the other hand, the same haplogroup is reported t o have elevated frequency in some complex diseases. To verify if centenaria ns clustered in a particular lineage within J we have sequenced the D-loop region from 18 centenarians and 18 younger controls, previously characteriz ed to be J. Then the entire mtDNA molecule was sequenced in a sub-sample of nine centenarians to find possible functional mutations associated with ha plogroup J in successful aging. No clustering of the J haplogroup mtDNA fro m centenarians was observed. In addition, most of the mutations found are k nown 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 Ne uropathy. This finding implies that the same mutations could predispose to disease or longevity, probably according to individual-specific genetic bac kgrounds and stochastic events. This data reveals another paradox of centen arians and confirms the complexity of the longevity trait.