Germline and somatic mtDNA mutations in mouse aging.

Autor: Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Nuria Marti-Gutierrez, Ying Li, Riffat Ahmed, Amy Koski, Eunju Kang, Hayley Darby, Thanasup Gonmanee, Younjung Park, Don P Wolf, Chong Jai Kim, Shoukhrat Mitalipov
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS ONE, Vol 13, Iss 7, p e0201304 (2018)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0201304
Popis: The accumulation of acquired mitochondrial genome (mtDNA) mutations with aging in somatic cells has been implicated in mitochondrial dysfunction and linked to age-onset diseases in humans. Here, we asked if somatic mtDNA mutations are also associated with aging in the mouse. MtDNA integrity in multiple organs and tissues in young and old (2-34 months) wild type (wt) mice was investigated by whole genome sequencing. Remarkably, no acquired somatic mutations were detected in tested tissues. However, we identified several non-synonymous germline mtDNA variants whose heteroplasmy levels (ratio of normal to mutant mtDNA) increased significantly with aging suggesting clonal expansion of inherited mtDNA mutations. Polg mutator mice, a model for premature aging, exhibited both germline and somatic mtDNA mutations whose numbers and heteroplasmy levels increased significantly with age implicating involvement in premature aging. Our results suggest that, in contrast to humans, acquired somatic mtDNA mutations do not accompany the aging process in wt mice.
Databáze: Directory of Open Access Journals
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