Open AccessThe co‐occurrence of mt DNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific
Author(s) -
Raule Nicola,
Sevini Federica,
Li Shengting,
Barbieri Annalaura,
Tallaro Federica,
Lomartire Laura,
Vianello Dario,
Montesanto Alberto,
Moilanen Jukka S.,
Bezrukov Vladyslav,
Blanché Hélène,
Hervonen Antti,
Christensen Kaare,
Deiana Luca,
Gonos Efstathios S.,
Kirkwood Tom B. L.,
Kristensen Peter,
Leon Alberta,
Pelicci Pier Giuseppe,
Poulain Michel,
Rea Irene M.,
Remacle Josè,
Robine Jean Marie,
Schreiber Stefan,
Sikora Ewa,
Eline Slagboom Peternella,
Spazzafumo Liana,
Antonietta Stazi Maria,
Toussaint Olivier,
Vaupel James W.,
Rose Giuseppina,
Majamaa Kari,
Perola Markus,
Johnson Thomas E.,
Bolund Lars,
Yang Huanming,
Passarino Giuseppe,
Franceschi Claudio
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12186
Subject(s) - biology , haplogroup , longevity , mitochondrial dna , genetics , human mitochondrial dna haplogroup , mutation , dna , gene , population , microbiology and biotechnology , genotype , haplotype , demography , sociology
Summary To re‐examine the correlation between mt DNA variability and longevity, we examined mt DNA s 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 mt DNA 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 mt DNA 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 mt DNA genes.