Age-related changes of mitochondrial structure and function in Caenorhabditis elegans

Yasuda, Kayo; Ishii, Takamasa; Suda, Hitoshi; Akatsuka, Akira; Hartman, Paul A.; Goto, Sataro; Miyazawa, Masaki; Ishii, Naoaki

doi:10.1016/j.mad.2006.07.002

Cited by 86 publications

(84 citation statements)

References 45 publications

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“…Mitochondrial decline and dysfunction are common features of aging and of many age‐dependent diseases in mammals and in model organisms including nematodes (Braeckman et al, 2002; Gruber et al, 2011; Herndon et al, 2002; López‐Otín, Blasco, Partridge, Serrano, & Kroemer, 2013; Yasuda et al, 2006). In humans, one of the mechanisms that is believed to be involved in mitochondrial aging is loss of mtDNA integrity and accumulation of mutant mtDNA (Stewart & Chinnery, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation and clonal expansion of mutant mtDNA are processes that have been causally linked to neurodegeneration and sarcopenia (Bender et al, 2006; Herbst et al, 2016). Metabolic decline, mitochondrial dysfunction, and sarcopenia are all conserved features of aging in C. elegans (Braeckman et al, 2002; Fisher, 2004; Gruber et al, 2011; Herndon et al, 2002; Yasuda et al, 2006). While some evidence for an age‐dependent increase in mtDNA deletion probability has been reported in C. elegans over 20 years ago, the question if these deletions are functionally linked to metabolic and mitochondrial aging has remained unanswered (Melov et al, 1994, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, according to one study, even in muscle of a 92‐year‐old individual, less than 1% of skeletal muscle fibers exhibited electron transport chain abnormalities and clonally expanded mtDNA deletions (Bua et al, 2006). For clonal expansion to significantly impact the 302 neurons or 187 muscle cells of an average adult C. elegans , let alone to explain the general decline in metabolic rate seen in aging nematodes (Braeckman et al, 2002; Gruber et al, 2011; Yasuda et al, 2006), the fraction of affected cells would have to far exceed the level seen even in the oldest humans (up to 30% of neurons) (Itoh, Weis, Mehraein, & Müller‐Höcker, 1996; Kraytsberg et al, 2006). For clonal expansion to impact a significant fraction of nematode cells, we would have to assume mtDNA half‐life values far shorter than even the most rapid mtDNA turnover rate previously suggested for any animal.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other animals, nematodes experience significant hypometabolism and decline in mitochondrial function as they age. Oxygen consumption and ATP levels (indicators of metabolism) significantly decline with age in nematodes (Braeckman, Houthoofd, & Vanfleteren, 2002; Gruber et al, 2011; Yasuda et al, 2006). Behaviors based on muscular and nervous system function, including pharyngeal pumping, spontaneous movement, and motility type, also decline rapidly with age in C. elegans (Collins, Huang, Hughes, & Kornfeld, 2008; Fisher, 2004; Gruber et al, 2011; Herndon et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…This age‐dependent deterioration of the C. elegans musculature resembles sarcopenia, involving muscle cell shrinkage, fraying, and loss of structure of muscle fibers with loosening of packing geometry of sarcomere fibers (Herndon et al, 2002). Aging in C. elegans is also associated with increased oxidative damage and loss of structural integrity of muscle mitochondria (Yasuda et al, 2006). …”

Section: Introductionmentioning

confidence: 99%

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Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long‐lived animals

Lakshmanan

Yee

et al. 2018

Aging Cell

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long‐lived animals

Lakshmanan

Yee

et al. 2018

Aging Cell

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Minimal Detection of Nuclear Mutations in XP‐V and Normal Cells Treated with Oxidative Stress Inducing Agents

Herman

Toffton

McCulloch

2014

J Biochem & Molecular Tox

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Elevated levels of reactive oxygen species (ROS) can be induced by exposure to various chemicals and radiation. One type of damage in DNA produced by ROS is modification of guanine to 7,8-dihydro-8-oxoguanine (8-oxoG). This particular alteration to the chemistry of the base can inhibit the replication fork and has been linked to mutagenesis, cancer and aging. In vitro studies have shown that the translesion synthesis polymerase, DNA polymerase η (pol η), is able to efficiently bypass 8-oxoG in DNA. In this study we wanted to investigate the mutagenic effects of oxidative stress, and in particular 8-oxoG, in the presence and absence of pol η. We quantified levels of oxidative stress, 8-oxoG levels in DNA, and nuclear mutation rates. We found that most of the 8-oxoG detected were localized to the mitochondrial DNA, opposed to the nuclear DNA. We also saw a corresponding lack of mutations in a nuclear encoded gene. This suggests that oxidative stress’ primary mutagenic effects are not predominantly on genomic DNA.

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In Vivo Visualization and Quantification of Mitochondrial Morphology in C. elegans

Boer

Smith

Vos

et al. 2021

Methods in Molecular Biology

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Age-related changes of mitochondrial structure and function in Caenorhabditis elegans

Cited by 86 publications

References 45 publications

Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long‐lived animals

Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long‐lived animals

Minimal Detection of Nuclear Mutations in XP‐V and Normal Cells Treated with Oxidative Stress Inducing Agents

In Vivo Visualization and Quantification of Mitochondrial Morphology in C. elegans

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