The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific.
Abstract
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.
Type
Journal articleSubject
genetics of longevitylongevity
mitochondrial DNA
mtDNA sequencing
oxidative phosphorylation
Aged, 80 and over
DNA, Mitochondrial
Female
Humans
Longevity
Male
Mutation
Oxidative Phosphorylation
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https://hdl.handle.net/10161/14698Published Version (Please cite this version)
10.1111/acel.12186Publication Info
Raule, Nicola; Sevini, Federica; Li, Shengting; Barbieri, Annalaura; Tallaro, Federica;
Lomartire, Laura; ... Franceschi, Claudio (2014). The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits,
not detected by haplogroup analysis, affects human longevity and is population specific.
Aging Cell, 13(3). pp. 401-407. 10.1111/acel.12186. Retrieved from https://hdl.handle.net/10161/14698.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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James Walton Vaupel
Research Professor Emeritus in the Sanford School of Public Policy
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