Please use this identifier to cite or link to this item: https://doi.org/10.1111/acel.12814
Title: Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long-lived animals
Authors: Lakshmanan L.N. 
Yee Z. 
Ng L.F. 
Gunawan R.
Halliwell B. 
Gruber J. 
Keywords: mitochondrial DNA
aging
animal
Caenorhabditis elegans
cell clone
gene deletion
genetics
half life time
longevity
Markov chain
mutation
nucleotide sequence
physiology
survival analysis
time factor
Aging
Animals
Base Sequence
Caenorhabditis elegans
Clone Cells
DNA, Mitochondrial
Half-Life
Longevity
Mutation
Sequence Deletion
Stochastic Processes
Survival Analysis
Time Factors
Issue Date: 2018
Citation: Lakshmanan L.N., Yee Z., Ng L.F., Gunawan R., Halliwell B., Gruber J. (2018). Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long-lived animals. Aging Cell 17 (5) : e12814. ScholarBank@NUS Repository. https://doi.org/10.1111/acel.12814
Abstract: Disruption of mitochondrial metabolism and loss of mitochondrial DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms of aging (López-Otín et al., Cell, 153, 2013 and 1194). Human aging is associated with loss in skeletal muscle mass and function (Sarcopenia), contributing significantly to morbidity and mortality. Muscle aging is associated with loss of mtDNA integrity. In humans, clonally expanded mtDNA deletions colocalize with sites of fiber breakage and atrophy in skeletal muscle. mtDNA deletions may therefore play an important, possibly causal role in sarcopenia. The nematode Caenorhabditis elegans also exhibits age-dependent decline in mitochondrial function and a form of sarcopenia. However, it is unclear if mtDNA deletions play a role in C. elegans aging. Here, we report identification of 266 novel mtDNA deletions in aging nematodes. Analysis of the mtDNA mutation spectrum and quantification of mutation burden indicates that (a) mtDNA deletions in nematode are extremely rare, (b) there is no significant age-dependent increase in mtDNA deletions, and (c) there is little evidence for clonal expansion driving mtDNA deletion dynamics. Thus, mtDNA deletions are unlikely to drive the age-dependent functional decline commonly observed in C. elegans. Computational modeling of mtDNA dynamics in C. elegans indicates that the lifespan of short-lived animals such as C. elegans is likely too short to allow for significant clonal expansion of mtDNA deletions. Together, these findings suggest that clonal expansion of mtDNA deletions is likely a private mechanism of aging predominantly relevant in long-lived animals such as humans and rhesus monkey and possibly in rodents. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Source Title: Aging Cell
URI: https://scholarbank.nus.edu.sg/handle/10635/175364
ISSN: 1474-9718
DOI: 10.1111/acel.12814
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