The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific.


Journal Article

To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes.

Full Text

Duke Authors

Cited Authors

  • Raule, N; Sevini, F; Li, S; Barbieri, A; Tallaro, F; Lomartire, L; Vianello, D; Montesanto, A; Moilanen, JS; Bezrukov, V; Blanché, H; Hervonen, A; Christensen, K; Deiana, L; Gonos, ES; Kirkwood, TBL; Kristensen, P; Leon, A; Pelicci, PG; Poulain, M; Rea, IM; Remacle, J; Robine, JM; Schreiber, S; Sikora, E; Eline Slagboom, P; Spazzafumo, L; Antonietta Stazi, M; Toussaint, O; Vaupel, JW; Rose, G; Majamaa, K; Perola, M; Johnson, TE; Bolund, L; Yang, H; Passarino, G; Franceschi, C

Published Date

  • June 2014

Published In

Volume / Issue

  • 13 / 3

Start / End Page

  • 401 - 407

PubMed ID

  • 24341918

Pubmed Central ID

  • 24341918

Electronic International Standard Serial Number (EISSN)

  • 1474-9726

International Standard Serial Number (ISSN)

  • 1474-9718

Digital Object Identifier (DOI)

  • 10.1111/acel.12186


  • eng