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Mitochondrial DNA Damage Patterns and Aging: Revising the Evidences for Humans and Mice.
Aging Dis. 2013 Sep 24;4(6):337-350. eCollection 2013. doi:
Kazachkova N, Ramos A, Santos C, Lima M
Abstract:
.....In this paper we revise the studies that analyze the association between patterns of mtDNA damage and aging, investigating putative alterations in mtDNA copy number as well as accumulation of deletions and of point mutations. Reports from the literature do not allow the establishment of a clear association between mtDNA copy number and age, either in humans or in mice. Further analysis, using a wide spectrum of tissues and a high number of individuals would be necessary to elucidate this pattern. Likewise humans, mice demonstrated a clear pattern of age-dependent and tissue-specific accumulation of mtDNA deletions. Deletions increase with age, and the highest amount of deletions has been observed in brain tissues both in humans and mice. On the other hand, mtDNA point mutations accumulation has been clearly associated with age in humans, but not in mice. Although further studies, using the same methodologies and targeting a larger number of samples would be mandatory to draw definitive conclusions, the revision of the available data raises concerns on the ability of mouse models to mimic the mtDNA damage patterns of humans, a fact with implications not only for the study of the aging process, but also for investigations of other processes in which mtDNA dysfunction is a hallmark, such as neurodegeneration.
PMID: 24307967
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843651/
Tags: animal models, mice, mtDNA, review