Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging?

Konstantin Khrapko, Yevgenya Kraytsberg, Aubrey D N J de Grey, Jan Vijg, Eric A. Schon

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Recent studies have demonstrated that transgenic mice with an increased rate of somatic point mutations in mitochondrial DNA (mtDNA mutator mice) display a premature aging phenotype reminiscent of human aging. These results are widely interpreted as implying that mtDNA mutations may be a central mechanism in mammalian aging. However, the levels of mutations in the mutator mice typically are more than an order of magnitude higher than typical levels in aged humans. Furthermore, most of the aging-like features are not specific to the mtDNA mutator mice, but are shared with several other premature aging mouse models, where no mtDNA mutations are involved. We conclude that, although mtDNA mutator mouse is a very useful model for studies of phenotypes associated with mtDNA mutations, the aging-like phenotypes of the mouse do not imply that mtDNA mutations are necessarily involved in natural mammalian aging. On the other hand, the fact that point mutations in aged human tissues are much less abundant than those causing premature aging in mutator mice does not mean that mtDNA mutations are not involved in human aging. Thus, mtDNA mutations may indeed be relevant to human aging, but they probably differ by origin, type, distribution, and spectra of affected tissues from those observed in mutator mice.

Original languageEnglish (US)
Pages (from-to)279-282
Number of pages4
JournalAging Cell
Volume5
Issue number3
DOIs
StatePublished - Jun 2006
Externally publishedYes

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Premature Aging
Mitochondrial DNA
Mutation
Phenotype
Point Mutation
Transgenic Mice

Keywords

  • Aging
  • Human
  • Mouse
  • mtDNA mutation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging? / Khrapko, Konstantin; Kraytsberg, Yevgenya; de Grey, Aubrey D N J; Vijg, Jan; Schon, Eric A.

In: Aging Cell, Vol. 5, No. 3, 06.2006, p. 279-282.

Research output: Contribution to journalArticle

Khrapko, Konstantin ; Kraytsberg, Yevgenya ; de Grey, Aubrey D N J ; Vijg, Jan ; Schon, Eric A. / Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging?. In: Aging Cell. 2006 ; Vol. 5, No. 3. pp. 279-282.
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