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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; [...]

The co‐occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific

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  • Medientyp: E-Artikel
  • Titel: The co‐occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific
  • Beteiligte: 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; [...]
  • Erschienen: Wiley, 2014
  • Erschienen in: Aging Cell
  • Sprache: Englisch
  • DOI: 10.1111/acel.12186
  • ISSN: 1474-9718; 1474-9726
  • Entstehung:
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  • Beschreibung: <jats:title>Summary</jats:title><jats:p>To re‐examine the correlation between mt<jats:styled-content style="fixed-case">DNA</jats:styled-content> variability and longevity, we examined mt<jats:styled-content style="fixed-case">DNA</jats:styled-content>s from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the <jats:styled-content style="fixed-case">GEHA EU</jats:styled-content> project. The samples were categorized by high‐resolution classification, while about 1300 mt<jats:styled-content style="fixed-case">DNA</jats:styled-content> 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<jats:styled-content style="fixed-case">DNA</jats:styled-content> mutations, including those that <jats:italic>per se</jats:italic> have a low, or very low, impact. In particular, the analysis of the mutations occurring in different <jats:styled-content style="fixed-case">OXPHOS</jats:styled-content> 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 <jats:styled-content style="fixed-case">OXPHOS</jats:styled-content> complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and <jats:styled-content style="fixed-case">III</jats:styled-content> (which also occurs in J subhaplogroups involved in <jats:styled-content style="fixed-case">LHON</jats:styled-content>) 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 <jats:styled-content style="fixed-case">DNA</jats:styled-content> variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mt<jats:styled-content style="fixed-case">DNA</jats:styled-content> genes.</jats:p>
  • Zugangsstatus: Freier Zugang