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 - 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
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 7
M1 - e0201304
ER -