The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific
N Raule
(1)
,
F Sevini
(1)
,
S Li
(2)
,
A Barbieri
(1)
,
F Tallaro
(3)
,
L Lomartire
(1)
,
D Vianello
(1)
,
A Montesanto
(3)
,
Js Moilanen
(4)
,
V Bezrukov
(5)
,
H Blanché
(6)
,
A Hervonen
(7)
,
K Christensen
(8)
,
L Deiana
(9)
,
Es Gonos
(10)
,
Tb Kirkwood
(11)
,
P Kristensen
(12)
,
A Leon
(13)
,
Pg Pelicci
(14)
,
M Poulain
(15)
,
Im Rea
(16)
,
J Remacle
(17)
,
Jean-Marie Robine
(18)
,
S Schreiber
(19)
,
E Sikora
(20)
,
Slagboom, P Eline
(21)
,
L Spazzafumo
(22)
,
Stazi, M Antonietta
(23)
,
O Toussaint
(24)
,
Jw Vaupel
(25)
,
G Rose
(3)
,
K Majamaa
(4)
,
M Perola
(26)
,
Te Johnson
(27)
,
L Bolund
(2)
,
H Yang
(2)
,
G Passarino
(3)
,
C Franceschi
(1)
1
UNIBO -
Alma Mater Studiorum Università di Bologna = University of Bologna
2 BGI - Beijing Genomics Institute [Shenzhen]
3 Unical - Università della Calabria [Arcavacata di Rende]
4 University of Oulu
5 Institute of Gerontology [Kiev]
6 Fondation Jean Dausset CEPH
7 University of Tampere [Finland]
8 SDU - University of Southern Denmark
9 UNISS - Università degli Studi di Sassari = University of Sassari [Sassari]
10 National Hellenic Research Foundation [Athens]
11 Newcastle University [Newcastle]
12 Aarhus University [Aarhus]
13 Research Innovation [Italy]
14 IFOM - IFOM, Istituto FIRC di Oncologia Molecolare
15 UCL - Université Catholique de Louvain = Catholic University of Louvain
16 QUB - Queen's University [Belfast]
17 Eppendorf Array Technologies S.A. [Namur]
18 CERMES3 - UMR 8211 / U988 / UM 7 - CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société
19 University Hospital Schleswig-Holstein [Kiel, Germany]
20 Nencki Institute of Experimental Biology
21 LUMC - Leiden University Medical Center
22 INRCA - Italian National Research Centre on Aging
23 ISS - Istituto Superiore di Sanità = National Institute of Health
24 FUNDP - Fondation Universitaire Notre Dame de la Paix
25 MPIDR - Max Planck Institute for Demographic Research
26 THL - National Public Health Institute [Finland]
27 University of Colorado [Boulder]
2 BGI - Beijing Genomics Institute [Shenzhen]
3 Unical - Università della Calabria [Arcavacata di Rende]
4 University of Oulu
5 Institute of Gerontology [Kiev]
6 Fondation Jean Dausset CEPH
7 University of Tampere [Finland]
8 SDU - University of Southern Denmark
9 UNISS - Università degli Studi di Sassari = University of Sassari [Sassari]
10 National Hellenic Research Foundation [Athens]
11 Newcastle University [Newcastle]
12 Aarhus University [Aarhus]
13 Research Innovation [Italy]
14 IFOM - IFOM, Istituto FIRC di Oncologia Molecolare
15 UCL - Université Catholique de Louvain = Catholic University of Louvain
16 QUB - Queen's University [Belfast]
17 Eppendorf Array Technologies S.A. [Namur]
18 CERMES3 - UMR 8211 / U988 / UM 7 - CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société
19 University Hospital Schleswig-Holstein [Kiel, Germany]
20 Nencki Institute of Experimental Biology
21 LUMC - Leiden University Medical Center
22 INRCA - Italian National Research Centre on Aging
23 ISS - Istituto Superiore di Sanità = National Institute of Health
24 FUNDP - Fondation Universitaire Notre Dame de la Paix
25 MPIDR - Max Planck Institute for Demographic Research
26 THL - National Public Health Institute [Finland]
27 University of Colorado [Boulder]
Jean-Marie Robine
- Fonction : Auteur
- PersonId : 746403
- IdHAL : jm-robine
- ORCID : 0000-0002-4111-6195
- IdRef : 031816533
Résumé
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.
Domaines
Sciences de l'Homme et SociétéFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific
|
Résumé |
en
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.
|
Auteur(s) |
N Raule
1
, F Sevini
1
, S Li
2
, A Barbieri
1
, F Tallaro
3
, L Lomartire
1
, D Vianello
1
, A Montesanto
3
, Js Moilanen
4
, V Bezrukov
5
, H Blanché
6
, A Hervonen
7
, K Christensen
8
, L Deiana
9
, Es Gonos
10
, Tb Kirkwood
11
, P Kristensen
12
, A Leon
13
, Pg Pelicci
14
, M Poulain
15
, Im Rea
16
, J Remacle
17
, Jean-Marie Robine
18
, S Schreiber
19
, E Sikora
20
, Slagboom, P Eline
21
, L Spazzafumo
22
, Stazi, M Antonietta
23
, O Toussaint
24
, Jw Vaupel
25
, G Rose
3
, K Majamaa
4
, M Perola
26
, Te Johnson
27
, L Bolund
2
, H Yang
2
, G Passarino
3
, C Franceschi
1
1
UNIBO -
Alma Mater Studiorum Università di Bologna = University of Bologna
( 30978 )
- Via Zamboni, 33 - 40126 Bologna
- Italie
2
BGI -
Beijing Genomics Institute [Shenzhen]
( 228027 )
- 11F, Bei Shan Industrial Zone Yantian District Shenzhen 518083
- Chine
3
Unical -
Università della Calabria [Arcavacata di Rende]
( 103704 )
- Campus di Arcavacata via Pietro Bucci 87036 Arcavacata di Rende (CS)
- Italie
4
University of Oulu
( 485794 )
- Finlande
5
Institute of Gerontology [Kiev]
( 1085761 )
- Ukraine
6
Fondation Jean Dausset CEPH
( 303322 )
-
- France
7
University of Tampere [Finland]
( 301029 )
- Kalevantie 4, Tampere
- Finlande
8
SDU -
University of Southern Denmark
( 50786 )
- 5320 Odense
- Danemark
9
UNISS -
Università degli Studi di Sassari = University of Sassari [Sassari]
( 568173 )
- via Vienna 2, 07100
Sassari,
- Italie
10
National Hellenic Research Foundation [Athens]
( 469482 )
- Grèce
11
Newcastle University [Newcastle]
( 252912 )
- Newcastle upon Tyne NE1 7RU
- Royaume-Uni
12
Aarhus University [Aarhus]
( 19908 )
- Nordre Ringgade 1 DK-8000 Aarhus C
- Danemark
13
Research Innovation [Italy]
( 1085764 )
- Italie
14
IFOM -
IFOM, Istituto FIRC di Oncologia Molecolare
( 117093 )
- Via Adamello 16, 20139 - Milan, Italy
- Italie
15
UCL -
Université Catholique de Louvain = Catholic University of Louvain
( 92863 )
- Place de l'Université 1 - 1348 Louvain-La-Neuve
- Belgique
16
QUB -
Queen's University [Belfast]
( 232128 )
- University Road, Belfast, BT7 1NN, Northern Ireland, UK
- Irlande
17
Eppendorf Array Technologies S.A. [Namur]
( 561850 )
- Rue de Seminaire, 22, Namur, Belgium
- Belgique
18
CERMES3 - UMR 8211 / U988 / UM 7 -
CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société
( 176631 )
- 7 rue Guy Môquet - BP 8 - 94801 Villejuif Cedex
Site administratif : Campus CNRS- 7, rue Guy Môquet- BP 8- 94801 Villejuif Cedex
Site Paris: CUSP (Centre universitaire des Saints-Pères)- Bâtiment Jacob (3ème étage)- 45, rue des Saints-Pères- 75270 Paris Cedex 06
- France
19
University Hospital Schleswig-Holstein [Kiel, Germany]
( 539463 )
- Allemagne
20
Nencki Institute of Experimental Biology
( 67943 )
- WARSAW
- Pologne
21
LUMC -
Leiden University Medical Center
( 300851 )
- Leids Universitair Medisch Centrum, Universiteit Leiden - 1233 ZA, Leiden
- Pays-Bas
22
INRCA -
Italian National Research Centre on Aging
( 547007 )
- Italie
23
ISS -
Istituto Superiore di Sanità = National Institute of Health
( 359183 )
- 299, Viale Regina Elena, 00161 – Roma
- Italie
24
FUNDP -
Fondation Universitaire Notre Dame de la Paix
( 87552 )
- rue Grandgagne 21 B-5000 NAMUR
- Belgique
25
MPIDR -
Max Planck Institute for Demographic Research
( 114184 )
- Konrad-Zuse-Straße 1, 18057 Rostock
- Allemagne
26
THL -
National Public Health Institute [Finland]
( 340388 )
- Mannerheimintie 166, Helsinki
- Finlande
27
University of Colorado [Boulder]
( 302215 )
- Boulder, Colorado 80309
- États-Unis
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2014
|
Volume |
13
|
Numéro |
3
|
Page/Identifiant |
401-407
|
Domaine(s) |
|
Mots-clés |
en
genetics of longevity, longevity, mitochondrial DNA, mtDNA sequencing, oxidative phosphorylation
|
DOI | 10.1111/acel.12186 |
Pubmed Id | 24341918 |
PubMed Central | PMC4326891 |
Fichier principal
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)
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