| Title: |
The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific |
| 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, Tb; Kristensen, P; Leon, A; Pelicci, Pg; Poulain, M; Rea, Im; Remacle, J; Robine, Jean-Marie; 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 |
| Contributors: |
Alma Mater Studiorum Università di Bologna = University of Bologna Bologne (UNIBO); Beijing Genomics Institute Shenzhen (BGI); Università della Calabria Arcavacata di Rende, Italia = University of Calabria Italy = Université de Calabre Italie (UniCal); University of Oulu Finland = Oulun yliopisto Suomi = Université d'Oulu Finlande; Institute of Gerontology Kiev; Fondation Jean Dausset - Centre d’Études du Polymorphisme Humain (CEPH); University of Tampere Finland; University of Southern Denmark = Syddansk Universitet (SDU); Università degli Studi di Sassari = University of Sassari (UNISS); National Hellenic Research Foundation Athens; Newcastle University Newcastle; Aarhus University Aarhus; Research Innovation Italy; IFOM, Istituto FIRC di Oncologia Molecolare (IFOM); Université Catholique de Louvain = Catholic University of Louvain (UCL); Queen's University Belfast (QUB); Eppendorf Array Technologies S.A. Namur; CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7); École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH); Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel (CAU); Nencki Institute of Experimental Biology; Polska Akademia Nauk = Polish Academy of Sciences = Académie polonaise des sciences (PAN); Leiden University Medical Center Leiden (LUMC); Universiteit Leiden = Leiden University; Italian National Research Centre on Aging (INRCA); Istituto Superiore di Sanità = National Institute of Health (ISS); Fondation Universitaire Notre Dame de la Paix (FUNDP); Facultés Universitaires Notre Dame de la Paix (FUNDP); Max Planck Institute for Demographic Research (MPIDR); Max-Planck-Gesellschaft; National Public Health Institute Finland (THL); University of Colorado Boulder |
| Source: |
ISSN: 1474-9726 ; Aging Cell ; https://cnrs.hal.science/hal-03478927 ; Aging Cell, 2014, 13 (3), pp.401-407. ⟨10.1111/acel.12186⟩. |
| Publisher Information: |
CCSD; Blackwell Publishing Ltd |
| Publication Year: |
2014 |
| Subject Terms: |
genetics of longevity; longevity; mitochondrial DNA; mtDNA sequencing; oxidative phosphorylation; [SHS]Humanities and Social Sciences |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/24341918; PUBMED: 24341918; PUBMEDCENTRAL: PMC4326891 |
| DOI: |
10.1111/acel.12186 |
| Availability: |
https://cnrs.hal.science/hal-03478927; https://cnrs.hal.science/hal-03478927v1/document; https://cnrs.hal.science/hal-03478927v1/file/Aging%20Cell%20-%202013%20-%20Raule%20-%20The%20co%E2%80%90occurrence%20of%20mtDNA%20mutations%20on%20different%20oxidative%20phosphorylation%20subunits%20%20not%20%281%29.pdf; https://doi.org/10.1111/acel.12186 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CA3B9630 |
| Database: |
BASE |