Abstract
The last 30. years of research greatly contributed to shed light on the role of mitochondrial DNA (mtDNA) variability in aging, although contrasting results have been reported, mainly due to bias regarding the population size and stratification, and to the use of analysis methods (haplogroup classification) that resulted to be not sufficiently adequate to grasp the complexity of the phenomenon.A 5-years European study (the GEHA EU project) collected and analyzed data on mtDNA variability on an unprecedented number of long-living subjects (enriched for longevity genes) and a comparable number of controls (matched for gender and ethnicity) in Europe. This very large study allowed a reappraisal of the role of both the inherited and the somatic mtDNA variability in aging, as an association with longevity emerged only when mtDNA variants in OXPHOS complexes co-occurred. Moreover, the availability of data from both nuclear and mitochondrial genomes on a large number of subjects paves the way for an evaluation at a very large scale of the epistatic interactions at a higher level of complexity.This scenario is expected to be even more clarified in the next future with the use of next generation sequencing (NGS) techniques, which are becoming applicable to evaluate mtDNA variability and, then, new mathematical/bioinformatic analysis methods are urgently needed. Recent advances of association studies on age-related diseases and mtDNA variability will also be discussed in this review, taking into account the bias hidden by population stratification. Finally, very recent findings in terms of mtDNA heteroplasmy (i.e. the coexistence of wild type and mutated copies of mtDNA) and aging as well as mitochondrial epigenetic mechanisms will also be discussed.
| Original language | English |
|---|---|
| Pages (from-to) | 234-244 |
| Number of pages | 11 |
| Journal | Experimental Gerontology |
| Volume | 56 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Epistasis
- Heteroplasmy
- Longevity
- Mitochondrial DNA
- MtDNA mutations
- Next generation sequencing
ASJC Scopus subject areas
- Ageing
- Biochemistry
- Cell Biology
- Endocrinology
- Genetics
- Molecular Biology
- Medicine(all)
Cite this
MtDNA mutations in human aging and longevity : Controversies and new perspectives opened by high-throughput technologies. / Sevini, Federica; Giuliani, Cristina; Vianello, Dario; Giampieri, Enrico; Santoro, Aurelia; Biondi, Fiammetta; Garagnani, Paolo; Passarino, Giuseppe; Luiselli, Donata; Capri, Miriam; Franceschi, Claudio; Salvioli, Stefano.
In: Experimental Gerontology, Vol. 56, 2014, p. 234-244.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MtDNA mutations in human aging and longevity
T2 - Controversies and new perspectives opened by high-throughput technologies
AU - Sevini, Federica
AU - Giuliani, Cristina
AU - Vianello, Dario
AU - Giampieri, Enrico
AU - Santoro, Aurelia
AU - Biondi, Fiammetta
AU - Garagnani, Paolo
AU - Passarino, Giuseppe
AU - Luiselli, Donata
AU - Capri, Miriam
AU - Franceschi, Claudio
AU - Salvioli, Stefano
PY - 2014
Y1 - 2014
N2 - The last 30. years of research greatly contributed to shed light on the role of mitochondrial DNA (mtDNA) variability in aging, although contrasting results have been reported, mainly due to bias regarding the population size and stratification, and to the use of analysis methods (haplogroup classification) that resulted to be not sufficiently adequate to grasp the complexity of the phenomenon.A 5-years European study (the GEHA EU project) collected and analyzed data on mtDNA variability on an unprecedented number of long-living subjects (enriched for longevity genes) and a comparable number of controls (matched for gender and ethnicity) in Europe. This very large study allowed a reappraisal of the role of both the inherited and the somatic mtDNA variability in aging, as an association with longevity emerged only when mtDNA variants in OXPHOS complexes co-occurred. Moreover, the availability of data from both nuclear and mitochondrial genomes on a large number of subjects paves the way for an evaluation at a very large scale of the epistatic interactions at a higher level of complexity.This scenario is expected to be even more clarified in the next future with the use of next generation sequencing (NGS) techniques, which are becoming applicable to evaluate mtDNA variability and, then, new mathematical/bioinformatic analysis methods are urgently needed. Recent advances of association studies on age-related diseases and mtDNA variability will also be discussed in this review, taking into account the bias hidden by population stratification. Finally, very recent findings in terms of mtDNA heteroplasmy (i.e. the coexistence of wild type and mutated copies of mtDNA) and aging as well as mitochondrial epigenetic mechanisms will also be discussed.
AB - The last 30. years of research greatly contributed to shed light on the role of mitochondrial DNA (mtDNA) variability in aging, although contrasting results have been reported, mainly due to bias regarding the population size and stratification, and to the use of analysis methods (haplogroup classification) that resulted to be not sufficiently adequate to grasp the complexity of the phenomenon.A 5-years European study (the GEHA EU project) collected and analyzed data on mtDNA variability on an unprecedented number of long-living subjects (enriched for longevity genes) and a comparable number of controls (matched for gender and ethnicity) in Europe. This very large study allowed a reappraisal of the role of both the inherited and the somatic mtDNA variability in aging, as an association with longevity emerged only when mtDNA variants in OXPHOS complexes co-occurred. Moreover, the availability of data from both nuclear and mitochondrial genomes on a large number of subjects paves the way for an evaluation at a very large scale of the epistatic interactions at a higher level of complexity.This scenario is expected to be even more clarified in the next future with the use of next generation sequencing (NGS) techniques, which are becoming applicable to evaluate mtDNA variability and, then, new mathematical/bioinformatic analysis methods are urgently needed. Recent advances of association studies on age-related diseases and mtDNA variability will also be discussed in this review, taking into account the bias hidden by population stratification. Finally, very recent findings in terms of mtDNA heteroplasmy (i.e. the coexistence of wild type and mutated copies of mtDNA) and aging as well as mitochondrial epigenetic mechanisms will also be discussed.
KW - Epistasis
KW - Heteroplasmy
KW - Longevity
KW - Mitochondrial DNA
KW - MtDNA mutations
KW - Next generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=84901831524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901831524&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2014.03.022
DO - 10.1016/j.exger.2014.03.022
M3 - Article
C2 - 24709341
AN - SCOPUS:84901831524
VL - 56
SP - 234
EP - 244
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
ER -