TY - JOUR
T1 - Germline and somatic mtDNA mutations in mouse aging
AU - Ma, Hong
AU - Lee, Yeonmi
AU - Hayama, Tomonari
AU - Van Dyken, Crystal
AU - Marti-Gutierrez, Nuria
AU - Li, Ying
AU - Ahmed, Riffat
AU - Koski, Amy
AU - Kang, Eunju
AU - Darby, Hayley
AU - Gonmanee, Thanasup
AU - Park, Younjung
AU - Wolf, Don P.
AU - Kim, Chong Jai
AU - Mitalipov, Shoukhrat
N1 - Funding Information:
The study was supported by grants from the National Institutes of Health R56AG045137 and P51OD011092, Burroughs Wellcome Fund, OHSU Institutional Funds, and National Research Foundation of Korea (NRF-2015K1A4A3046807). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge the Small Lab Animal Unit and Molecular & Cellular Biology Support Core at Oregon National Primate Research Center of OHSU for providing expertise and services. We are grateful to Drs. Nils-Göran Larsson and James Stewart for providing Polg mice and Taosheng Huang for consulting on MiSeq. We are indebted to Yibing Jia for help in whole mtDNA genome sequencing.
Publisher Copyright:
© 2018 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0201304
DO - 10.1371/journal.pone.0201304
M3 - Article
C2 - 30040856
AN - SCOPUS:85050404713
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e0201304
ER -