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Mitochondrial mutations and aging: random drift is insufficient to explain the accumulation of mitochondrial deletion mutants in short-lived animals

Lookup NU author(s): Dr Axel Kowald, Emeritus Professor Thomas Kirkwood

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Abstract

Mitochondrial DNA deletions accumulate over the life course in post-mitotic cells of many species and may contribute to aging. Often a single mutant expands clonally and finally replaces the wild-type population of a whole cell. One proposal to explain the driving force behind this accumulation states that random drift alone, without any selection advantage, is sufficient to explain the clonal accumulation of a single mutant. Existing mathematical models show that such a process might indeed work for humans. However, to be a general explanation for the clonal accumulation of mtDNA mutants, it is important to know whether random drift could also explain the accumulation process in short-lived species like rodents. To clarify this issue, we modelled this process mathematically and performed extensive computer simulations to study how different mutation rates affect accumulation time and the resulting degree of heteroplasmy. We show that random drift works for lifespans of around 100years, but for short-lived animals, the resulting degree of heteroplasmy is incompatible with experimental observations.

Publication metadata

Author(s): Kowald A, Kirkwood TBL

Publication type: Article

Publication status: Published

Journal: Aging Cell

Year: 2013

Volume: 12

Issue: 4

Pages: 728-731

Print publication date: 01/08/2013

Online publication date: 07/06/2013

Acceptance date: 10/05/2013

Date deposited: 04/11/2014

ISSN (print): 1474-9718

ISSN (electronic): 1474-9726

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/acel.12098

DOI: 10.1111/acel.12098

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