The DOI matches its Crossref record; 273 of the 276 references it cites were found in a registry or an index; none of the 188 sources its claims cite is checked for support yet.
Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases
Open accessAbstract
As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mitochondrial dysfunction, such as decreased electron transport chain (ETC) enzyme activity and impaired cellular respiration. We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases. Additionally, interventions to improve mitochondrial function and attenuate the symptoms of aging are examined.
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TL;DR
This review argues that clonally expanded mtDNA mutations arising from errors by the nuclear-encoded mtDNA replication machinery, rather than ROS-induced damage, are a major driving force behind aging and age-related diseases. It surveys Pol γ, PolG2, Twinkle, TFAM, MGME1, and RNase H1, linking their dysfunction to mtDNA mutagenesis, mitochondrial dysfunction, and diseases such as PEO and Parkinson’s disease.
Key findings
- mtDNA mutation rates are estimated at 10- to 17-fold higher than nuclear DNA, and over 85% of mutations detected in vivo could be recapitulated in vitro by purified human Pol γ, suggesting spontaneous replication errors account for most base-pair substitutions in mtDNA.
- The exonuclease-deficient Pol γ mtDNA mutator mouse shows a 3- to 8-fold increase in somatic point mutations, a 2000-fold higher mutation load than wild-type by random capture, and a 90-fold increase in circular mtDNA with large deletions excluding one hotspot; it develops a progeroid phenotype, whereas heterozygous mice have a 500-fold higher mutational burden than age-matched wild-type controls but no progeroid phenotype or reduced lifespan.
- Disease-associated replication-machinery defects include over 300 POLG mutations; PEO-associated Pol γ mutations R943H and Y955C cause a 99% decrease in polymerase activity, Y955C causes a 45-fold decrease in dNTP binding affinity, and G923D and A957S retain 21% and 23% of wild-type catalytic activity, respectively.
- Twinkle has 31 dominant and 3 recessive mutations recognized, mostly causing age-related disease; TFAM, MGME1, and RNase H1 defects are also linked to mtDNA depletion, replication stalling, PEO, neurodegeneration, or embryonic lethality in model systems.
Methods
- Narrative review of the literature on mtDNA replication machinery, mtDNA mutagenesis, aging, and age-related diseases.
- Synthesizes evidence from in vitro biochemistry, cultured cells, mouse models, Drosophila, C. elegans, and human patient studies.
- No systematic search strategy, inclusion/exclusion criteria, or meta-analysis is described.
Limitations
- The paper states that future studies focused on mechanisms of action are needed to effectively delay aging and prevent age-related diseases.
- The paper states that it remains controversial whether point mutations, deletions, or both drive the progeroid phenotype in mtDNA mutator mice, and that the timing of mtDNA mutations remains debated.
- Evident from the text: this is a narrative review without systematic methods, and many conclusions rely on animal models or correlative human data rather than uniform causal evidence.
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Claims the paper makes
130 Not checked yet · 33 Own interpretation · 13 No basis given
In the paper
“Preliminary data suggests that mtDNA shifting also occurs in aging skeletal muscle following resistance exercise training (Tarnopolsky, 2009).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
What the sources say
- Not checked yetcites Tarnopolsky, 2009 source
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In the paper
“Here, we showed that deficiency and/or dysfunction in many of the nuclear-encoded mtDNA replication proteins, including Pol γ, PolG2, Twinkle, TFAM, MGME1 and RNase H1, results in age-related diseases and/or phenotypes both in vitro and in vivo.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 10. Conclusion
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In the paper
“Of the 17 human cellular DNA polymerases, polymerase gamma (Pol γ) is the only replicative polymerase known to function in mitochondrial DNA replication and repair (Bebenek and Kunkel, 2004; Ropp and Copeland, 1996; Sweasy et al., 2006).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 2. Mitochondrial biology and genetics
What the sources say
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In the paper
“Accumulations of mtDNA damage in the form of point mutations, deletions and depletions are correlated with aging and age-related diseases as observed in human skeletal muscle (Bua et al., 2006; Fayet et al., 2002), liver (Yen et al., 1991), brain (Corral-Debrinski et al., 1992a; Corral-Debrinski et al., 1994; Lin et al., 2002), heart (Corral-Debrinski et al., 1992b; Cortopassi and Arnheim, 1990),”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
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In the paper
“Early reports comparing nucleotide substitutions in mtDNA from somatic tissues of different primates revealed a 10-fold higher rate of evolution for mtDNA relative to the nuclear genome (Brown et al., 1979; Brown et al., 1982), implying a relatively high mutation rate for mtDNA.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
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In the paper
“In particular, much of the mtDNA damage is linked with the nuclear-encoded proteins responsible for its replication.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 1. Introduction
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In the paper
“We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > Abstract
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In the paper
“Conversely, G:C to T:A transversions are only a small fraction of the mutations found in aged Drosophila (Itsara et al., 2014) or humans (Kennedy et al., 2013; Zheng et al., 2006).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The most common oxidative lesions in mtDNA are the G:C to T:A transversion mutations caused by adenine pairing with the guanine adduct 7,8-dihydro-8-oxo-deoxyguanosine (8-oxo-dG) (Wang et al., 1998).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Wang et al., 1998 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Correlative evidence between increased levels of 8-oxo-dG and age-related deletions in mtDNA from humans (Capel et al., 2005; Hayakawa et al., 1992; Hayakawa et al., 1991), mice (Vermulst et al., 2007), rats (Sawada and Carlson, 1987) and houseflies (Sohal and Sohal, 1991) has been reported.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
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In the paper
“The catalytic subunit has DNA polymerase, 3′→5′ exonuclease and 5′-dRP lyase activities (Graziewicz et al., 2006; Kaguni, 2004).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 2. Mitochondrial biology and genetics
What the sources say
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In the paper
“Over-expression of genes involved in the maintenance of thiol redox homeostasis or co-overexpression of Cu-Zn superoxide dismutase (Cu-ZnSOD) and catalase increase the lifespan of Drosophila melanogaster by 33–48% (Orr et al., 2013; Orr and Sohal, 1994).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Orr et al., 2013 source
- Not checked yetcites Orr and Sohal, 1994
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In the paper
“As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > Abstract
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, this suggests that ROS and 8-oxo-dG are not major contributors to mtDNA mutations in WT organisms.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
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In the paper
“When either Cu-ZnSOD or catalase is over-expressed individually, only Cu-ZnSOD extends lifespan up to 48% while catalase has neutral or slightly negative effects (Sun and Tower, 1999).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Sun and Tower, 1999
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In the paper
“For example, mice deficient in either Cu-ZnSOD or MnSOD have widespread oxidative damage and hepatocarcinogenesis or neurodegeneration with reduced lifespan (Elchuri et al., 2005; Lebovitz et al., 1996).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, when human catalase is localized to peroxisomes or targeted to the nucleus in mice, no detectable reduction in mtDNA damage or significant extension of lifespan are observed (Schriner and Linford, 2006; Schriner et al., 2000).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Schriner and Linford, 2006
- Not checked yetcites Schriner et al., 2000 source
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In the paper
“These same mice are also protected from mitochondrial dysfunction, decreased energy metabolism and lipid-induced insulin resistance in skeletal muscle (Lee et al., 2010).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Lee et al., 2010 source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > Abstract
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It encodes 37 mitochondrial genes: 22 transfer RNAs, 2 mitochondrial ribosomal RNAs and 13 proteins subunits of ETC complexes, with the exception of Complex II which is entirely nuclear encoded.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 2. Mitochondrial biology and genetics
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“The ogg1 or ogg1/mth1 knock-out mice have 20-fold higher levels of 8-oxoguanine in mtDNA (de Souza-Pinto et al., 2001) and half the life expectancy relative to wild-type (WT) mice (Xie et al., 2004), but no increase in mtDNA mutations (Halsne et al., 2012).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Pol γ holoenzyme is a heterotrimer consisting of a single 140 kDa catalytic subunit (nuclear encoded by POLG at chromosomal locus 15q25) and a 55 kDa accessory subunit that forms a dimer (nuclear encoded by POLG2 at chromosomal locus 17q24.1).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 2. Mitochondrial biology and genetics
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Human mtDNA is maternally inherited (Giles et al., 1980) and exists as a circular, double-stranded genome organized into 16,569 base pairs.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 2. Mitochondrial biology and genetics
What the sources say
- Not checked yetcites Giles et al., 1980 source
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Newer theories associate aging and mitochondrial dysfunction with clonally expanded mtDNA mutations caused by replication errors and altered mitochondrial dynamics.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 1. Introduction
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In the paper
“Support for the classical Mitochondrial Free Radical Theory of Aging (MFRTA) waned as new evidence linked ROS to both toxicity and signaling pathways associated with longevity.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 1. Introduction
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Kujoth et al. (2005) found no biomarkers of ROS induced damage to DNA, proteins or lipids, but report that tissue dysfunction is the result of apoptosis.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Kujoth et al., 2005 source
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As ROS gradually increase over time, so do the cumulative levels of mtDNA damages, with ROS eventually reaching unstoppable toxic concentrations resulting in further mitochondrial dysfunction and aging.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
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In the paper
“Trifunovic et al. (2004) also describe impaired OXPHOS with a reduction in ETC enzyme activities and decreased ATP production.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Trifunovic et al., 2004 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, while SOD knock-out mice (Sod2−/−) die within the first 10 days of life (Li et al., 1995), heterozygous mice (Sod2+/−) are viable with longevity and OXPHOS activity comparable to WT mice (Mansouri et al., 2006).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Li et al., 1995
- Not checked yetcites Mansouri et al., 2006 source
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In the paper
“In this theory, high levels of ROS promote mtDNA damage and the aged phenotype, while low levels of ROS are signaling molecules that regulate stress response pathways and activate cellular processes that enhance lifespan (Hekimi et al., 2011).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Hekimi et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In a follow-up study to experimentally address the “vicious” cycle aspect of the MFRTA, mouse embryonic fibroblasts from mtDNA mutator mice are shown to produce normal amounts of ROS and demonstrate no increased sensitivity to oxidative stress (Trifunovic et al., 2005).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Trifunovic et al., 2005 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“On the other hand, inactivation of any of the five isoforms of SOD in Caenorhabditis elegans fails to decrease longevity, in spite of increased oxidative stress, and actually prolongs lifespan (Van Raamsdonk and Hekimi, 2012).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 3. MtDNA damage in aging: ROS versus replication errors
What the sources say
- Not checked yetcites Van Raamsdonk and Hekimi, 2012
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Exonuclease-deficient Pol γ pancreatic islet cells caused impaired glucose tolerance, diabetes, and increased apoptosis in β-cells (Bensch et al., 2007; Bensch et al., 2009).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 4. Fidelity of DNA synthesis by pol γ
What the sources say
- Not checked yetcites Bensch et al., 2007 source
- Not checked yetcites Bensch et al., 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The mice appear normal through adolescence but develop a progeroid phenotype including alopecia (hair loss) and graying, kyphosis (curvature of the spine), osteoporosis (loss of bone density), sarcopenia (loss of muscle mass), weight loss, reduced subcutaneous fat, presbycusis (hearing loss), reduced fertility, anemia, cardiac hypertrophy (heart enlargement), and a reduced lifespan.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Unlike the homozygous mtDNA mutator mice, mice heterozygous for the Pol γ mutation have no progeroid phenotype or reduced lifespan (Kujoth et al., 2005; Trifunovic et al., 2004).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There are also no changes in the levels of antioxidants, protein carbonyls or aconitase enzyme activity in their tissues.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Trifunovic et al., 2005 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“WT and heterozygous mice mainly accumulate deletions at one hotspot between two 15-bp direct repeats, whereas homozygous mutant mice accumulate deletions regardless of the presence of direct repeats (Vermulst et al., 2008).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Vermulst et al., 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, using an adaptation of the more sensitive “random capture method,” which relies on PCR amplification of single molecules for mutation detection but is not limited by polymerase fidelity, the heterozygous mice are found to have a 500-fold higher mutational burden than age-matched wild-type controls and a 30-fold increase over the oldest wild-type animals (Vermulst et al., 2007).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Vermulst et al., 2007 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Of the handful of heterozygous mutations identified in POLG2, G451E (Longley et al., 2006) and R369G (Craig et al., 2012; Young et al., 2011) are linked to PEO.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The resulting amino acid substitutions impair the stability of the ETC complexes, resulting in OXPHOS deficiency.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Edgar et al., 2009
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“To date, there are over 300 disease-associated mutations in POLG listed in the Human DNA Polymerase Gamma Mutation Database (http://tools.niehs.nih.gov/polg).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
- Not checked yetcites http://tools.niehs.nih.gov/polg
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“PEO manifests during adulthood and is characterized by bilateral ptosis and progressive weakening of the external eye muscles, proximal muscle weakness and wasting, skeletal muscle with ragged red fibers, impaired ETC enzyme activity, exercise intolerance, sensory ataxic neuropathy and respiratory failure due to muscle fatigue.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a transgenic mouse model, human Pol γ encoding Y955C was targeted to the heart. These mice develop a molecular signature of PEO in the heart with cardiomyopathy, loss of mtDNA, increased 8-OHdG and premature death (Lewis et al., 2007).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
- Not checked yetcites Lewis et al., 2007 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Most of the mutations in Pol γ are associated with arPEO. They are compound heterozygotes and often occur with common Pol γ mutations, such as A467T (Van Goethem et al., 2003a), W748S (Van Goethem et al., 2004), R309L (Lamantea et al., 2002), G848S (Lamantea et al., 2002), R627W (Van Goethem et al., 2003a), N846S (Van Goethem et al., 2003c) or T251I in cis with P587L (Lamantea et al., 2002; Scud”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Both R943H and Y955C alter direct interactions with incoming dNTPs resulting in severely decreased processivity and a 99% decrease in polymerase activity.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
- Not checked yetcites Graziewicz et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Therefore, these fragments are surmised to arise from stalled replication due to Pol γ exonuclease deficiency and do not contribute to the progeroid phenotype (Kukat and Trifunovic, 2009).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Kukat and Trifunovic, 2009
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In 2001, a heterozygous mutation in Pol γ that substituted a tyrosine with cysteine at codon 955 (Y955C) was first identified as a disease locus for adPEO while three more missense mutations were associated with arPEO (Van Goethem et al., 2001).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
- Not checked yetcites Van Goethem et al., 2001 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Two sisters with early-onset PD, peripheral neuropathy and without PEO had a 37% decrease in mtDNA content with multiple deletions and were found to be compound heterozygous for two missense mutations (G737R and R853W) in Pol γ (Davidzon et al., 2006).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
- Not checked yetcites Davidzon et al., 2006 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The Y955C mutation has a wild-type catalytic rate, but a 45-fold decrease in binding affinity for the incoming dNTP.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
What the sources say
- Not checked yetcites Ponamarev et al., 2002 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with arPEO have the same clinical features as with adPEO, but with greater variation in symptoms and time of onset.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Edgar et al. (2009) reported frequent point mutations in ETC genes in homozygous mtDNA mutator mice, while heterozygous mice were not examined.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 5. Exonuclease-deficient pol γ mouse links mtDNA mutations and deletions to aging
What the sources say
- Not checked yetcites Edgar et al., 2009
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Some associated diseases manifest in adulthood and include symptoms of aging, namely autosomal dominant and recessive forms of Progressive External Ophthalmoplegia (adPEO/arPEO) and Parkinson’s disease.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.1. DNA Polymerase γ
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests Twinkle provides cardioprotection and could be a potential therapy for heart failure patients.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A complete POLG2 knock-out is embryonic lethal in mice, but the heterozygous knockout (+/−) mouse has a normal phenotype (Humble et al., 2013).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
What the sources say
- Not checked yetcites Humble et al., 2013 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Twinkle is essential for mtDNA maintenance and copy number (Tyynismaa et al., 2004).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Tyynismaa et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Knockdown of porcine oocyte PolG2 causes an aging-like phenotype as evidenced by decreased production of ATP and maturation promoting factor (MPF), reducing the fraction of oocytes that reach MII stage (Lee et al., 2015).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
What the sources say
- Not checked yetcites Lee et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Homodimeric mutants have problems stimulating PolG processivity, with G451E being more severely defective than R396G (Craig et al., 2012; Longley et al., 2006; Young et al., 2011).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The N-terminal domain is important for ssDNA binding and stimulation of the C-terminal helicase activity (Farge et al., 2007).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Farge et al., 2007 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was classified as a helicase based on sequence similarity to bacteriophage T7 gene 4 primase-helicase (T7 gp4) (Spelbrink et al., 2001).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Spelbrink et al., 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“MGME1 interacts directly with PolG suggesting a role in mtDNA replication, likely providing 5′ → 3′ exonuclease activity (Nicholls et al., 2014).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.5. Mitochondrial Genome Maintenance Exonuclease 1 (MGME1)
What the sources say
- Not checked yetcites Nicholls et al., 2014 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“G451E homodimers also fail to enhance binding of PolG to DNA, while R369G has weaker binding to PolG.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Helicase activity along with strand annealing activity has been confirmed (Sen et al., 2012), but no primase activity has been detected to date.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Sen et al., 2012 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Twinkle has two domains, a primase-like N-terminal domain and a C-terminal helicase domain (Shutt and Gray, 2006).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Shutt and Gray, 2006
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Twinkle is a 72 kDA hexamer/heptamer that functions as a 5′ → 3′ helicase for mtDNA replication (Korhonen et al., 2003).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Korhonen et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is involved in D-loop formation and localizes to the nucleoid (Jemt et al., 2015; Milenkovic et al., 2013; Spelbrink et al., 2001).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In adult human hearts however, mtDNA has been shown to exist as dimers and is organized into highly complex, branched molecules (Pohjoismaki et al., 2009).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Pohjoismaki et al., 2009 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Knockdown of RNase H1 in human bone osteosarcoma cells (143B TK-) led to lower mtDNA copy number and complete stalling of replication (Ruhanen et al., 2011), suggesting RNase H1 is vital for mtDNA replication.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.6. Ribonuclease H1 (RNase H1)
What the sources say
- Not checked yetcites Ruhanen et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In all, 31 dominant and 3 recessive mutations have been recognized, the majority of which cause age-related disease (Sanchez-Martinez et al., 2012; Spelbrink et al., 2001).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Depletion of any of one these proteins results in severe dysfunction in respiratory capacity and fragmentation of mitochondria (Chen et al., 2005; Chen et al., 2010; Song et al., 2009)”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 8. Mitochondrial dynamics and aging
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Overexpression of adPEO Twinkle mutations in HEK293 cells cause an accumulation of replication intermediates suggesting that these mutations are triggering replication stalling (Goffart et al., 2009; Wanrooij et al., 2007).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Originally, it was shown that CR decreases ROS production in rodents, particularly at Complex I, thereby preventing oxidative damage in mitochondria from heart (Gredilla et al., 2002), liver (Lopez-Torres et al., 2002), skeletal muscle (Lass et al., 1998) and brain (Sanz et al., 2005).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, others have reported that although oxidative capacity is improved, there are no changes in the mtDNA mutation load (Jeppesen et al., 2009; Taivassalo et al., 2006).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This activation is accomplished with either eccentric or concentric resistance exercise, as shown in a patient with the G12315A tRNAleu(CUN) point mutation, where resistance training significantly improved heteroplasmic ratios and increased the number of respiratory-competent fibers in muscle fibers (Taivassalo et al., 1999).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
What the sources say
- Not checked yetcites Taivassalo et al., 1999 source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, CR induces mitochondrial biogenesis and increases respiration through activation of sirtuin 1 (SIRT1), an NAD+-dependent histone deacetylase, and its downstream induction of PGC-1α (Chistiakov et al., 2014; Martin-Montalvo and de Cabo, 2013).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
What the sources say
- Not checked yetcites Chistiakov et al., 2014 source
- Not checked yetcites Martin-Montalvo and de Cabo, 2013
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Fusion and fission are opposing actions that work together to maintain the number, size, shape and function of mitochondria (Chan, 2012).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 8. Mitochondrial dynamics and aging
What the sources say
- Not checked yetcites Chan, 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“As with the fission and fusion processes, insufficient mitophagy and autophagy contribute to the accumulation of mutant mtDNA and are a factor in aging and age-related diseases (Gaziev et al., 2014; Green et al., 2011; Hubbard et al., 2012; Rubinsztein et al., 2011).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 8. Mitochondrial dynamics and aging
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CR has been shown to extend both medium and maximum lifespan and delay the onset of age-related diseases in a variety of species, including yeast (Kaeberlein et al., 2007), C. elegans (Lee et al., 2006), rodents (Masoro, 2009) and Rhesus monkeys (Colman et al., 2014).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For all the targeted cell types, TFAM depletion leads to mtDNA depletion (not reported for midbrain DA neurons), mitochondrial transcript depletion (not reported for midbrain DA neurons) and respiratory chain deficiency, suggesting that TFAM is essential for mtDNA maintenance in vivo”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.4. Transcription Factor A of Mitochondria (TFAM)
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Aging is a multifactorial, progressive, biological process with mitochondria playing a central role.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 10. Conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The MFRTA, once at the forefront of aging theory, has lost favor since its fundamental notion of a “vicious” cycle of ROS generating ETC disruption, and hence more ROS, is based on anecdotal evidence.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 10. Conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Using Digital Deletion Detection (3D), a newer technology that allows for the study of rare, low occurring mtDNA deletions, Taylor et al. (2014) report that although the total deletion load increases in human brain with aging, the number and diversity of deletions remains constant.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 7. The contribution of clonal expansion of mtDNA mutations to mitochondrial dysfunction
What the sources say
- Not checked yetcites Taylor et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another mouse model system crossed mice overexpressing TFAM with the mito-mice that have mutant mtDNA carrying a deletion of 4696 bp leading to an overall increase in mtDNA content and copy number without a decrease in the amount of deleted mtDNA (Nishiyama et al., 2010).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.4. Transcription Factor A of Mitochondria (TFAM)
What the sources say
- Not checked yetcites Nishiyama et al., 2010 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The deletor mouse phenotypes can be attenuated with a lipid-lowering agent, such as bezafibrate, however this treatment causes severe hepatic side effects (Yatsuga and Suomalainen, 2012).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Yatsuga and Suomalainen, 2012
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TFAM overexpression in rat pancreatic islet cells normalized Nd1 mRNA levels and restored glucose-induced ATP generation along with insulin secretion (Gauthier et al., 2009).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.4. Transcription Factor A of Mitochondria (TFAM)
What the sources say
- Not checked yetcites Gauthier et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TFAM deletion in mouse pyramidal neurons causes mitochondrial late-onset neurodegeneration (MILON) (Sorensen et al., 2001) whereas deletion in mouse midbrain DA neurons leads to PD (Ekstrand et al., 2007).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.4. Transcription Factor A of Mitochondria (TFAM)
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This mouse attenuates VO-induced eccentric hypertrophy and improves cardiac function while suppressing the production of mitochondrial ROS and subsequent redox-sensitive signals (Ikeda et al., 2015).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.3. Twinkle
What the sources say
- Not checked yetcites Ikeda et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This does not imply that high levels of ROS do not contribute to the aging phenotype through oxidative damage to cellular components, such as proteins and lipids.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 10. Conclusion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
The mtDNA mutator mouse progeroid phenotype is a valid model of mammalian aging.
“However, the first strong experimental evidence demonstrating a causal relationship between aging and the accumulation of mtDNA mutations/deletions secondary to an exonuclease-deficient Pol γ was obtained with the creation of the mtDNA mutator mouse.”
The paper relies on this without support.
MtDNA typically exists as monomeric double-stranded, covalently closed circles.
“MtDNA typically exists as monomeric double-stranded, covalently closed circles.”
The paper relies on this without support.
The theory of mitohormesis states that low levels of ROS are important signaling molecules that regulate stress response pathways and enhance longevity.
“The theory of mitohormesis states that low levels of ROS are important signaling molecules that regulate stress response pathways and enhance longevity.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The oxidation of EF-Tu could lead to altered function and the incorrect translation of mitochondrial proteins, which include 13 components of the electron transport chain [78].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [78]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
“Of the handful of heterozygous mutations identified in POLG2, G451E (Longley et al., 2006) and R369G (Craig et al., 2012; Young et al., 2011) are linked to PEO.”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 6. Age-related mitochondrial diseases associated with defective mtDNA replication machinery > 6.2. PolG2
“Homodimeric mutants have problems stimulating PolG processivity, with G451E being more severely defective than R396G (Craig et al., 2012; Longley et al., 2006; Young et al., 2011).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > 9. Interventions to attenuate the symptoms of aging
“However, acute exercise in rats increased mRNA expression of Mnf1 and Mfn2 24 hours post-exercise (Cartoni et al., 2005).”
§ Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases > References
“23. Cartoni R Leger B Hock MB Praz M Crettenand A Pich S Ziltener JL Luthi F Deriaz O Zorzano A Gobelet C Kralli A Russell AP 2005 Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise The Journal of physiology 567 349 358 15961417 PMC1474174”
Citations
Cites
3 retracted
Safdar, A., Bourgeois, J. M., Ogborn, D. I., Little, J. P., Hettinga, B. P., Akhtar, M., Thompson, J. E., Melov, S., Mocellin, N. J., Kujoth, G. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019581108 · Cited by 320
RetractedEndurance exercise is protective for mice with mitochondrial myopathy
Wenz, T., Diaz, F., Hernandez, D., & Moraes, C. T. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91571.2008 · Cited by 78
RetractedRETRACTED ARTICLE:Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice
Safdar, A., Khrapko, K., Flynn, J. M., Saleem, A., Lisio, M. D., Johnston, A. P. W., Kratysberg, Y., Samjoo, I. A., Kitaoka, Y., Ogborn, D. I., et al. (2015) · Skeletal Muscle · doi:10.1186/s13395-016-0075-9 · Cited by 68
RetractedAging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
Parkinson's disease: clinical features and diagnosis
Jankovic, J. (2008) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2007.131045 · Cited by 5,720
Rapid evolution of animal mitochondrial DNA
Brown, W. M., George, M., & Wilson, A. C. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.4.1967 · Cited by 3,439
Oxidative DNA damage: mechanisms, mutation, and disease
Cooke, M. S., Evans, M. D., Dizdaroglu, M., & Lunec, J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0752rev · Cited by 3,245
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107
The Biologic Clock: The Mitochondria?
Harman, D. (1972) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1972.tb00787.x · Cited by 2,026
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase
Li, Y., Huang, T.-T., Carlson, E. J., Melov, S., Ursell, P. C., Olson, J. L., Noble, L. J., Yoshimura, M. P., Berger, C., Chan, P. H., et al. (1995) · Nature Genetics · doi:10.1038/ng1295-376 · Cited by 1,789
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724
Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594
Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1769 · Cited by 1,570
Mitochondrial DNA sequences of primates: tempo and mode of evolution
Brown, W. M., Prager, E. M., Wang, A., & Wilson, A. C. (1982) · Journal of Molecular Evolution · doi:10.1007/bf01734101 · Cited by 1,554
Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases
Chen, H., & Chan, D. C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp326 · Cited by 1,506
Orr, W. C., & Sohal, R. S. (1994) · Science · doi:10.1126/science.8108730 · Cited by 1,461
Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction
Chen, H., Chomyn, A., & Chan, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503062200 · Cited by 1,376
Maternal inheritance of human mitochondrial DNA.
Giles, R. E., Blanc, H., Cann, H. M., & Wallace, D. C. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.11.6715 · Cited by 1,365
Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging
Green, D. R., Galluzzi, L., & Kroemer, G. (2011) · Science · doi:10.1126/science.1201940 · Cited by 1,245
Chen, H., Vermulst, M., Wang, Y. E., Chomyn, A., Prolla, T. A., McCaffery, J. M., & Chan, D. C. (2010) · Cell · doi:10.1016/j.cell.2010.02.026 · Cited by 1,211
Fusion and fission: interlinked processes critical for mitochondrial health
Chan, D. C. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110410-132529 · Cited by 1,196
Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis
Lee, Y.-J., Jeong, S.-Y., Karbowski, M., Smith, C. L., & Youle, R. J. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-04-0294 · Cited by 1,042
Lebovitz, R. M., Zhang, H., Vogel, H., Cartwright, J., Dionne, L., Lu, N., Huang, S., & Matzuk, M. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9782 · Cited by 1,023
Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases
Linnane, A., Ozawa, T., Marzuki, S., & Tanaka, M. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92145-4 · Cited by 983
Transcriptional control of mitochondrial biogenesis: the central role of PGC-1
Ventura-Clapier, R., Garnier, A., & Veksler, V. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn098 · Cited by 932
Mitochondrial transcription factor A regulates mtDNA copy number in mammals
Ekstrand, M. I. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh109 · Cited by 919
Kraytsberg, Y., Kudryavtseva, E., McKee, A. C., Geula, C., Kowall, N. W., & Khrapko, K. (2006) · Nature Genetics · doi:10.1038/ng1778 · Cited by 896
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C. (1992) · Nature Genetics · doi:10.1038/ng1292-324 · Cited by 890
Spelbrink, J. N., Li, F.-Y., Tiranti, V., Nikali, K., Yuan, Q.-P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., et al. (2001) · Nature Genetics · doi:10.1038/90058 · Cited by 882
Ribonuclease H: the enzymes in eukaryotes
Cerritelli, S. M., & Crouch, R. J. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06908.x · Cited by 845
Van Goethem, G., Dermaut, B., Löfgren, A., Martin, J.-J., & Van Broeckhoven, C. (2001) · Nature Genetics · doi:10.1038/90034 · Cited by 841
Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790
Detection of a specific mitochondrial DNA deletion in tissues of older humans
Cortopassi, G. A., & Arnheim, N. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.23.6927 · Cited by 788
Van Remmen, H., Ikeno, Y., Hamilton, M., Pahlavani, M., Wolf, N., Thorpe, S. R., Alderson, N. L., Baynes, J. W., Epstein, C. J., Huang, T.-T., et al. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00122.2003 · Cited by 734
Michikawa, Y., Mazzucchelli, F., Bresolin, N., Scarlato, G., & Attardi, G. M. (1999) · Science · doi:10.1126/science.286.5440.774 · Cited by 724
Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys
Colman, R. J., Beasley, T. M., Kemnitz, J. W., Johnson, S. C., Weindruch, R., & Anderson, R. M. (2014) · Nature Communications · doi:10.1038/ncomms4557 · Cited by 711
Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency
López-Lluch, G., Hunt, N., Jones, B., Zhu, M., Jamieson, H., Hilmer, S., Cascajo, M. V., Allard, J., Ingram, D. K., Navas, P., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510452103 · Cited by 699
Mitochondrial DNA mutations and human disease
Tuppen, H. A. L., Blakely, E. L., Turnbull, D. M., & Taylor, R. W. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.005 · Cited by 676
Mitochondrial fusion, fission and autophagy as a quality control axis: The bioenergetic view
Twig, G., Hyde, B. B., & Shirihai, O. S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.05.001 · Cited by 674
Elchuri, S., Oberley, T. D., Qi, W., Eisenstein, R. S., Jackson Roberts, L., Van Remmen, H., Epstein, C. J., & Huang, T.-T. (2005) · Oncogene · doi:10.1038/sj.onc.1208207 · Cited by 667
Zeviani, M., Servidei, S., Gellera, C., Bertini, E., DiMauro, S., & DiDonato, S. (1989) · Nature · doi:10.1038/339309a0 · Cited by 636
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., Rizza, R. A., Coenen-Schimke, J. M., & Nair, K. S. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1888 · Cited by 631
Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion
Song, Z., Ghochani, M., McCaffery, J. M., Frey, T. G., & Chan, D. C. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-03-0252 · Cited by 623
Taking a good look at free radicals in the aging process
Hekimi, S., Lapointe, J., & Wen, Y. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.06.008 · Cited by 606
Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons
Ekstrand, M. I., Terzioglu, M., Galter, D., Zhu, S., Hofstetter, C., Lindqvist, E., Thams, S., Bergstrand, A., Hansson, F. S., Trifunovic, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605208103 · Cited by 605
Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production
Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A. T., Dufour, E., Khvorostov, I., Spelbrink, J. N., Wibom, R., Jacobs, H. T., & Larsson, N.-G. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508886102 · Cited by 555
Hayashi, J., Ohta, S., Kikuchi, A., Takemitsu, M., Goto, Y., & Nonaka, I. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10614 · Cited by 553
Similarity of Human Mitochondrial Transcription Factor 1 to High Mobility Group Proteins
Parisi, M. A., & Clayton, D. A. (1991) · Science · doi:10.1126/science.2035027 · Cited by 548
Luoma, P., Melberg, A., Rinne, J. O., Kaukonen, J. A., Nupponen, N. N., Chalmers, R. M., Oldfors, A., Rautakorpi, I., Peltonen, L., Majamaa, K., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16983-3 · Cited by 548
Emerging functions of mammalian mitochondrial fusion and fission
Chen, H., & Chan, D. C. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi270 · Cited by 538
Mitochondrial DNA mutations in human colonic crypt stem cells
Taylor, R. W., Barron, M. J., Borthwick, G. M., Gospel, A., Chinnery, P. F., Samuels, D. C., Taylor, G. A., Plusa, S. M., Needham, S. J., Greaves, L. C., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci19435 · Cited by 530
New insights into the role of mitochondria in aging: mitochondrial dynamics and more
Seo, A. Y., Joseph, A.-M., Dutta, D., Hwang, J. C. Y., Aris, J. P., & Leeuwenburgh, C. (2010) · Journal of Cell Science · doi:10.1242/jcs.070490 · Cited by 522
Heteroplasmic mitochondrial DNA mutations in normal and tumour cells
He, Y., Wu, J., Dressman, D. C., Iacobuzio–Donahue, C. A., Markowitz, S. D., Velculescu, V. E., Diaz, L. A., Kinzler, K. W., Vogelstein, B., & Papadopoulos, N. (2010) · Nature · doi:10.1038/nature08802 · Cited by 516
Mitochondrial Aging and Age-Related Dysfunction of Mitochondria
Chistiakov, D. A., Sobenin, I. A., Revin, V. V., Orekhov, A. N., & Bobryshev, Y. V. (2014) · BioMed Research International · doi:10.1155/2014/238463 · Cited by 497
Campbell, C. T., Kolesar, J. E., & Kaufman, B. A. (2012) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2012.03.002 · Cited by 477
Age and aerobic exercise training effects on whole body and muscle protein metabolism
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., & Nair, K. S. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00366.2003 · Cited by 470
Sun, J., & Tower, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.216 · Cited by 467
Reijns, M. A. M., Rabe, B., Rigby, R. E., Mill, P., Astell, K. R., Lettice, L. A., Boyle, S., Leitch, A., Keighren, M., Kilanowski, F., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.011 · Cited by 466
Mutagenicity and repair of oxidative DNA damage: insights from studies using defined lesions
Wang, D., Kreutzer, D. A., & Essigmann, J. M. (1998) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(98)00066-9 · Cited by 464
Bua, E., Johnson, J., Herbst, A., Delong, B., McKenzie, D., Salamat, S., & Aiken, J. M. (2006) · The American Journal of Human Genetics · doi:10.1086/507132 · Cited by 442
Wang, J., Wilhelmsson, H., Graff, C., Li, H., Oldfors, A., Rustin, P., Brüning, J. C., Kahn, C. R., Clayton, D. A., Barsh, G. S., et al. (1999) · Nature Genetics · doi:10.1038/5089 · Cited by 435
Silva, J. P., Köhler, M., Graff, C., Oldfors, A., Magnuson, M. A., Berggren, P.-O., & Larsson, N.-G. (2000) · Nature Genetics · doi:10.1038/81649 · Cited by 433
Nakada, K., Inoue, K., Ono, T., Isobe, K., Ogura, A., Goto, Y., Nonaka, I., & Hayashi, J. (2001) · Nature Medicine · doi:10.1038/90976 · Cited by 430
Ono, T., Isobe, K., Nakada, K., & Hayashi, J.-I. (2001) · Nature Genetics · doi:10.1038/90116 · Cited by 420
DNA Polymerase γ, The Mitochondrial Replicase
Kaguni, L. S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161455 · Cited by 414
DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice
Vermulst, M., Wanagat, J., Kujoth, G. C., Bielas, J. H., Rabinovitch, P. S., Prolla, T. A., & Loeb, L. A. (2008) · Nature Genetics · doi:10.1038/ng.95 · Cited by 411
Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise
Cartoni, R., Léger, B., Hock, M. B., Praz, M., Crettenand, A., Pich, S., Ziltener, J., Luthi, F., Dériaz, O., Zorzano, A., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.092031 · Cited by 406
Mitochondrial point mutations do not limit the natural lifespan of mice
Vermulst, M., Bielas, J. H., Kujoth, G. C., Ladiges, W. C., Rabinovitch, P. S., Prolla, T. A., & Loeb, L. A. (2007) · Nature Genetics · doi:10.1038/ng1988 · Cited by 404
Composition and dynamics of human mitochondrial nucleoids.
Garrido, N., Griparić, L., Jokitalo, E., Wartiovaara, J., van der Bliek, A. M., & Spelbrink, J. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-07-0399 · Cited by 390
High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain
Lin, M. T. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.2.133 · Cited by 366
Kennedy, S. R., Salk, J. J., Schmitt, M. W., & Loeb, L. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003794 · Cited by 363
On the origin of the β cellPreprint
Oliver-Krasinski, J. M., & Stoffers, D. A. (2008) · Genes & Development · doi:10.1101/gad.1670808 · Cited by 361
Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease
Corral‐Debrinski, M., Shoffner, J. M., Lott, M. T., & Wallace, D. C. (1992) · Mutation Research/DNAging · doi:10.1016/0921-8734(92)90021-g · Cited by 360
Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice
Cerritelli, S. M., Frolova, E. G., Feng, C., Grinberg, A., Love, P. E., & Crouch, R. J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00088-1 · Cited by 358
Mitochondrial DNA repair and aging
Mandavilli, B. S., Santos, J. H., & Houten, B. V. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00220-8 · Cited by 345
Tyynismaa, H., Mjosund, K. P., Wanrooij, S., Lappalainen, I., Ylikallio, E., Jalanko, A., Spelbrink, J. N., Paetau, A., & Suomalainen, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505551102 · Cited by 342
Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age
Elson, J. L., Samuels, D. C., Turnbull, D. M., & Chinnery, P. F. (2001) · The American Journal of Human Genetics · doi:10.1086/318801 · Cited by 340
Superoxide dismutase is dispensable for normal animal lifespan
Raamsdonk, J. M. V., & Hekimi, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116158109 · Cited by 337
Miller, F. J. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng060 · Cited by 332
de Souza-Pinto, N. C., Eide, L., Hogue, B. A., Thybo, T., Stevnsner, T., Seeberg, E. C., Klungland, A., & Bohr, V. A. (2001) · PubMed · Cited by 325
Lee, H.-Y., Choi, C. S., Birkenfeld, A. L., Alves, T. C., Jornayvaz, F. R., Jurczak, M. J., Zhang, D., Woo, D. K., Shadel, G. S., Ladiges, W., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.004 · Cited by 319
Marked changes in mitochondrial DNA deletion levels in Alzheimer brains
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., McKee, A. C., Beal, M. F., Graham, B. H., & Wallace, D. C. (1994) · Genomics · doi:10.1006/geno.1994.1525 · Cited by 309
Dietary deprivation extends lifespan in Caenorhabditis elegans
Lee, G. D., Wilson, M. A., Zhu, M., Wolkow, C. A., De Cabo, R., Ingram, D. K., & Zou, S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00241.x · Cited by 307
Increased mitochondrial mass in mitochondrial myopathy mice
Wredenberg, A., Wibom, R., Wilhelmsson, H., Graff, C., Wiener, H. H., Burden, S. J., Oldfors, A., Westerblad, H., & Larsson, N.-G. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.232591499 · Cited by 302
DNA Polymerase γ in Mitochondrial DNA Replication and Repair
Graziewicz, M. A., Longley, M. J., & Copeland, W. C. (2006) · Chemical Reviews · doi:10.1021/cr040463d · Cited by 301
Self-citationMitochondrial myopathy induces a starvation-like response
Tyynismaa, H., Carroll, C. J., Raimundo, N., Ahola-Erkkilä, S., Wenz, T., Ruhanen, H., Guse, K., Hemminki, A., Peltola-Mjøsund, K. E., Tulkki, V., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq310 · Cited by 300
Korhonen, J. A., Gaspari, M., & Falkenberg, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306981200 · Cited by 298
Hydrogen peroxide release by mitochondria increases during aging
Sohal, R. S., & Sohal, B. H. (1991) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(91)90034-w · Cited by 296
Xie, Y., Yang, H., Cunanan, C., Okamoto, K., Shibata, D., Pan, J., Barnes, D. E., Lindahl, T., McIlhatton, M., Fishel, R., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3834 · Cited by 291
Cloning and Characterization of the Human Mitochondrial DNA Polymerase, DNA Polymerase γ
Ropp, P. A., & Copeland, W. C. (1996) · Genomics · doi:10.1006/geno.1996.0490 · Cited by 284
Self-citationAge-associated oxygen damage and mutations in mitochondrial DNA in human hearts
Hayakawa, M., Hattori, K., Sugiyama, S., & Ozawa, T. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)92300-m · Cited by 283
Müller‐Höcker, J. (1989) · PubMed Central · Cited by 280
López-Torres, M., Gredilla, R., Sanz, A., & Barja, G. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00773-6 · Cited by 277
Kwong, L. K., & Sohal, R. S. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1495 · Cited by 273
Ikeuchi, M., Matsusaka, H., Kang, D., Matsushima, S., Ide, T., Kubota, T., Fujiwara, T., Hamasaki, N., Takeshita, A., Sunagawa, K., et al. (2005) · Circulation · doi:10.1161/circulationaha.104.524835 · Cited by 273
Longley, M. J., Nguyen, D., Kunkel, T. A., & Copeland, W. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105230200 · Cited by 270
Self-citationLamantea, E., Tiranti, V., Bordoni, A., Toscano, A., Bono, F., Servidei, S., Papadimitriou, A., Spelbrink, H., Silvestri, L., Casari, G., et al. (2002) · Annals of Neurology · doi:10.1002/ana.10278 · Cited by 270
Grumati, P., Coletto, L., Schiavinato, A., Castagnaro, S., Bertaggia, E., Sandri, M., & Bonaldo, P. (2011) · Autophagy · doi:10.4161/auto.7.12.17877 · Cited by 267
Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle
Drake, J. C., Wilson, R. J., & Yan, Z. (2016) · The FASEB Journal · doi:10.1096/fj.15-276337 · Cited by 263
POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement
Van Goethem, G., Luoma, P., Rantamäki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Löfgren, A., Martin, J. J., De Jonghe, P., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000140494.58732.83 · Cited by 261
Stein, H., & Hausen, P. (1969) · Science · doi:10.1126/science.166.3903.393 · Cited by 259
Bebenek, K., & Kunkel, T. A. (2004) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(04)69005-x · Cited by 258
Fisher, R. P., Topper, J. N., & Clayton, D. A. (1987) · Cell · doi:10.1016/0092-8674(87)90220-0 · Cited by 256
Ngo, H., Lovely, G. A., Phillips, R., & Chan, D. C. (2014) · Nature Communications · doi:10.1038/ncomms4077 · Cited by 254
Lass, A., Sohal, B. H., Weindruch, R. H., Forster, M. J., & Sohal, R. S. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00144-0 · Cited by 251
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number
Tyynismaa, H., Sembongi, H., Bokori-Brown, M., Granycome, C., Ashley, N., Poulton, J., Jalanko, A., Spelbrink, J. N., Holt, I. J., & Suomalainen, A. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh342 · Cited by 250
Ageing-associated 5 kb deletion in human liver mitochondrial DNA
Yen, T.-C., Su, J.-H., King, K.-L., & Wei, Y.-H. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91788-e · Cited by 248
Mutant POLG2 Disrupts DNA Polymerase γ Subunits and Causes Progressive External Ophthalmoplegia
Longley, M. J., Clark, S., Yu Wai Man, C., Hudson, G., Durham, S. E., Taylor, R. W., Nightingale, S., Turnbull, D. M., Copeland, W. C., & Chinnery, P. F. (2006) · The American Journal of Human Genetics · doi:10.1086/504303 · Cited by 248
Goethem, G. V., Martin, J. J., Dermaut, B., Löfgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Zandijcke, M. V., Moonen, M., et al. (2003) · Neuromuscular Disorders · doi:10.1016/s0960-8966(02)00216-x · Cited by 245
Is Cell Aging Caused by Respiration-Dependent Injury to the Mitochondrial Genome?
Fleming, J. E., Miquel, J., Cottrell, S. F., Yengoyan, L. S., & Economos, A. C. (2009) · Gerontology · doi:10.1159/000212510 · Cited by 242
Early‐onset familial parkinsonism due to POLG mutations
Davidzon, G., Greene, P., Mancuso, M., Klos, K. J., Ahlskog, J. E., Hirano, M., & DiMauro, S. (2006) · Annals of Neurology · doi:10.1002/ana.20831 · Cited by 239
Recent developments in yeast aging
Kaeberlein, M., Burtner, C. R., & Kennedy, B. K. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030084 · Cited by 239
Sawada, M., & Carlson, J. C. (1987) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(87)90057-1 · Cited by 238
Kornblum, C., Nicholls, T. J., Haack, T. B., Schöler, S., Peeva, V., Danhauser, K., Hallmann, K., Zsurka, G., Rorbach, J., Iuso, A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2501 · Cited by 232
Longley, M. J., Prasad, R., Srivastava, D., Wilson, S. H., & Copeland, W. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12244 · Cited by 228
Self-citationMansouri, A., Muller, F. L., Liu, Y., Ng, R., Faulkner, J., Hamilton, M., Richardson, A., Huang, T.-T., Epstein, C. J., & Van Remmen, H. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.11.004 · Cited by 227
Lim, S. E., Longley, M. J., & Copeland, W. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.53.38197 · Cited by 226
Mitochondrial DNA in Aging and Disease
Wallace, D. C. (1997) · Scientific American · doi:10.1038/scientificamerican0897-40 · Cited by 222
Ahlqvist, K. J., Hämäläinen, R. H., Yatsuga, S., Uutela, M., Terzioglu, M., Götz, A., Forsström, S., Salven, P., Angers-Loustau, A., Kopra, O. H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.11.012 · Cited by 221
Taivassalo, T., Gardner, J. L., Taylor, R. W., Schaefer, A. M., Newman, J., Barron, M. J., Haller, R. G., & Turnbull, D. M. (2006) · Brain · doi:10.1093/brain/awl282 · Cited by 220
Fisher, R. P., & Clayton, D. A. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39184-6 · Cited by 217
Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy
Jeppesen, T. D., Schwartz, M., Olsen, D. B., Wibrand, F., Krag, T., Duno, M., Hauerslev, S., & Vissing, J. (2006) · Brain · doi:10.1093/brain/awl149 · Cited by 211
Fayet, G., Jansson, M., Sternberg, D., Moslemi, A.-R., Blondy, P., Lombès, A., Fardeau, M., & Oldfors, A. (2002) · Neuromuscular Disorders · doi:10.1016/s0960-8966(01)00332-7 · Cited by 206
Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm
Hayakawa, M., Torii, K., Sugiyama, S., Tanaka, M., & Ozawa, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91921-x · Cited by 199
Edgar, D., Shabalina, I., Camara, Y., Wredenberg, A., Calvaruso, M. A., Nijtmans, L., Nedergaard, J., Cannon, B., Larsson, N.-G., & Trifunovic, A. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.06.010 · Cited by 195
Spelbrink, J. N., Toivonen, J. M., Hakkaart, G. A. J., Kurkela, J. M., Cooper, H. M., Lehtinen, S. K., Lecrenier, N., Back, J. W., Speijer, D., Foury, F., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000559200 · Cited by 193
Luo, L., Lu, A.-M., Wang, Y., Hong, A., Chen, Y., Hu, J., Li, X., & Qin, Z.-H. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.02.009 · Cited by 192
Ultra-deep sequencing of mouse mitochondrial DNA: mutational patterns and their origins
Ameur, A., Stewart, J. B., Freyer, C., Hagström, E., Ingman, M., Larsson, N.-G., & Gyllensten, U. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002028 · Cited by 187
Konopka, A. R., Suer, M. K., Wolff, C. A., & Harber, M. P. (2014) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glt107 · Cited by 187
Genetic modification of survival in tissue-specific knockout mice with mitochondrial cardiomyopathy
Li, H., Wang, J., Wilhelmsson, H., Hansson, A., Thorén, P., Duffy, J., Rustin, P., & Larsson, N.-G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3467 · Cited by 185
Hayashi, Y., Yoshida, M., Yamato, M., Ide, T., Wu, Z., Ochi-Shindou, M., Kanki, T., Kang, D., Sunagawa, K., Tsutsui, H., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1957-08.2008 · Cited by 181
Pagnamenta, A. T., Taanman, J., Wilson, C. J., Anderson, N. E., Marotta, R., Duncan, A., Bitner-Glindzicz, M. A. K., Taylor, R. W., Laskowski, A., Thorburn, D. R., et al. (2006) · Human Reproduction · doi:10.1093/humrep/del076 · Cited by 175
Kang, C., Chung, E., Diffee, G., & Ji, L. L. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.08.004 · Cited by 174
Oxidative stress is not a major contributor to somatic mitochondrial DNA mutations
Itsara, L. S., Kennedy, S. R., Fox, E. J., Yu, S., Hewitt, J. J., Sanchez-Contreras, M., Cardozo-Pelaez, F., & Pallanck, L. J. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1003974 · Cited by 173
Milenkovic, D., Matic, S., Kuhl, I., Ruzzenente, B., Freyer, C., Jemt, E., Park, C. B., Falkenberg, M., & Larsson, N.-G. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt051 · Cited by 173
Oxidative Modification of Proteins: Age-Related Changes
Chakravarti, B., & Chakravarti, D. N. (2006) · Gerontology · doi:10.1159/000097865 · Cited by 172
Ohtani, N., Haruki, M., Morikawa, M., Crouch, R. J., Itaya, M., & Kanaya, S. (1998) · Biochemistry · doi:10.1021/bi982207z · Cited by 172
Greaves, L. C., Nooteboom, M., Elson, J. L., Tuppen, H. A. L., Taylor, G. A., Commane, D. M., Arasaradnam, R. P., Khrapko, K., Taylor, R. W., Kirkwood, T. B. L., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004620 · Cited by 172
Díaz, F. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf602 · Cited by 171
Morpho-dynamic changes of mitochondria during ageing of human endothelial cells
Jendrach, M., Pohl, S., Vöth, M., Kowald, A., Hammerstein, P., & Bereiter‐Hahn, J. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.002 · Cited by 170
Mitochondrial DNA mutations in neurodegeneration
Keogh, M. J., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.015 · Cited by 169
Müller-Höcker, J., Seibel, P., Schneiderbanger, K., & Kadenbach, B. (1993) · Virchows Archiv A Pathological Anatomy and Histopathology · doi:10.1007/bf01605127 · Cited by 168
Sörensen, L., Ekstrand, M., Silva, J., Lindqvist, E., Xu, B., Rustin, P., Olson, L., & Larsson, N.-G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08082.2001 · Cited by 167
Sanz, A., Caro, P., Ibañez, J., Gómez, J., Gredilla, R., & Barja, G. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-4131-0 · Cited by 165
Calorie restriction mimetics: Can you have your cake and eat it, too?
Ingram, D. K., & Roth, G. S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.005 · Cited by 164
Resistance training in patients with single, large-scale deletions of mitochondrial DNA
Murphy, J. L., Blakely, E. L., Schaefer, A. M., He, L., Wyrick, P. S., Haller, R. G., Taylor, R. W., Turnbull, D. M., & Taivassalo, T. (2008) · Brain · doi:10.1093/brain/awn252 · Cited by 164
Joseph, A.-M., Adhihetty, P. J., Wawrzyniak, N. R., Wohlgemuth, S. E., Picca, A., Kujoth, G. C., Prolla, T. A., & Leeuwenburgh, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069327 · Cited by 161
Goethem, G. V., Schwartz, M., Löfgren, A., Dermaut, B., Broeckhoven, C. V., & Vissing, J. (2003) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201002 · Cited by 161
Gene shifting: a novel therapy for mitochondrial myopathy
Taivassalo, T. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.6.1047 · Cited by 160
Ponamarev, M. V., Longley, M. J., Nguyen, D., Kunkel, T. A., & Copeland, W. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200100200 · Cited by 156
Self-citationMitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease
Luoma, P. T., Eerola, J., Ahola, S., Hakonen, A. H., Hellström, O., Kivistö, K. T., Tienari, P. J., & Suomalainen, A. (2007) · Neurology · doi:10.1212/01.wnl.0000276955.23735.eb · Cited by 154
Testa, G., Biasi, F., Poli, G., & Chiarpotto, E. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660699 · Cited by 153
Mitochondria and PGC-1α in Aging and Age-Associated Diseases
Wenz, T. (2011) · Journal of Aging Research · doi:10.4061/2011/810619 · Cited by 152
Ikeda, M., Ide, T., Fujino, T., Arai, S., Saku, K., Kakino, T., Tyynismaa, H., Yamasaki, T., Yamada, K.-I., Kang, D., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0119687 · Cited by 152
Carrodeguas, J. A., Theis, K., Bogenhagen, D. F., & Kisker, C. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00153-8 · Cited by 150
Recent mitochondrial DNA mutations increase the risk of developing common late-onset human diseases
Hudson, G., Gomez-Duran, A., Wilson, I. J., & Chinnery, P. F. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004369 · Cited by 148
Wanrooij, S., Goffart, S., Pohjoismäki, J. L. O., Yasukawa, T., & Spelbrink, J. N. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm215 · Cited by 148
Mitochondrial genome maintenance in health and disease
Copeland, W. C., & Longley, M. J. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.03.010 · Cited by 147
Self-citationOrigins of human mitochondrial point mutations as DNA polymerase γ-mediated errors
Zheng, W., Khrapko, K., Coller, H. A., Thilly, W. G., & Copeland, W. C. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.12.012 · Cited by 141
Self-citationCombined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age
Irving, B. A., Lanza, I. R., Henderson, G. C., Rao, R. R., Spiegelman, B. M., & Nair, K. S. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3081 · Cited by 139
Dietary restriction.; mitochondrial function and aging: From yeast to humans
Ruetenik, A., & Barrientos, A. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.005 · Cited by 139
Goffart, S., Cooper, H. M., Tyynismaa, H., Wanrooij, S., Suomalainen, A., & Spelbrink, J. N. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddn359 · Cited by 138
High mitochondrial DNA copy number has detrimental effects in mice
Ylikallio, E., Tyynismaa, H., Tsutsui, H., Ide, T., & Suomalainen, A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq163 · Cited by 136
Cabelof, D. C. (2003) · DNA repair · doi:10.1016/s1568-7864(02)00219-7 · Cited by 133
Effect of bezafibrate treatment on late-onset mitochondrial myopathy in mice
Yatsuga, S., & Suomalainen, A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr482 · Cited by 133
Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age
Cottrell, D. A., Blakely, E. L., Johnson, M. A., Ince, P. G., Borthwick, G. M., & Turnbull, D. M. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00234-7 · Cited by 132
Graziewicz, M. A., Longley, M. J., Bienstock, R. J., Zeviani, M., & Copeland, W. C. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb805 · Cited by 131
Self-citationCaloric restriction and genomic stability
Heydari, A. R., Unnikrishnan, A., Ventrella-Lucente, L. F., & Richardson, A. G. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm860 · Cited by 127
Evolution of the mitochondrial fusion–fission cycle and its role in aging
Kowald, A., & Kirkwood, T. B. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101604108 · Cited by 126
Construction of transgenic mice with tissue-specific acceleration of mitochondrial DNA mutagenesis
Zhang, D., Mott, J. L., Chang, S.-W., Denniger, G., Feng, Z., & Zassenhaus, H. P. (2000) · Genomics · doi:10.1006/geno.2000.6333 · Cited by 124
Pohjoismäki, J. L. O., Goffart, S., Tyynismaa, H., Willcox, S., Ide, T., Kang, D., Suomalainen, A., Karhunen, P. J., Griffith, J. D., Holt, I. J., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016600 · Cited by 122
Jemt, E., Persson, Ö., Shi, Y., Mehmedovic, M., Uhler, J. P., Dávila López, M., Freyer, C., Gustafsson, C. M., Samuelsson, T., & Falkenberg, M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv804 · Cited by 121
Lewis, W., Day, B. J., Kohler, J. J., Hosseini, S. H., Chan, S. S. L., Green, E. C., Haase, C. P., Keebaugh, E. S., Long, R., Ludaway, T., et al. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700523 · Cited by 121
Self-citationCaloric restriction-induced life extension of rats and mice: A critique of proposed mechanisms
Masoro, E. J. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.02.011 · Cited by 120
RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy
Reyes, A., Melchionda, L., Nasca, A., Carrara, F., Lamantea, E., Zanolini, A., Lamperti, C., Fang, M., Zhang, J., Ronchi, D., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.05.013 · Cited by 115
Zhang, D. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00695-8 · Cited by 115
Gauthier, B. R., Wiederkehr, A., Baquié, M., Dai, C., Powers, A. C., Kerr-Conte, J., Pattou, F., MacDonald, R. J., Ferrer, J., & Wollheim, C. B. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.07.002 · Cited by 115
Shutt, T. E., & Gray, M. W. (2006) · Journal of Molecular Evolution · doi:10.1007/s00239-005-0162-8 · Cited by 111
Hirano, M., Marti, R., Ferreiro-Barros, C., Vilà, M. R., Tadesse, S., Nishigaki, Y., Nishino, I., & Vu, T. H. (2001) · Seminars in Cell & Developmental Biology · doi:10.1006/scdb.2001.0279 · Cited by 109
Autophagic response to exercise training in skeletal muscle with age
Kim, Y. A., Kim, Y. S., Oh, S. L., Kim, H.-J., & Song, W. (2013) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0246-7 · Cited by 108
Capel, F., Rimbert, V., Lioger, D., Diot, A., Rousset, P., Mirand, P. P., Boirie, Y., Morio, B., & Mosoni, L. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.11.001 · Cited by 108
Bori, Z., Zhao, Z., Koltai, E., Fatouros, I. G., Jamurtas, A. Z., Douroudos, I. I., Terzis, G., Chatzinikolaou, A., Sovatzidis, A., Draganidis, D., et al. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.03.004 · Cited by 108
Mitochondria: A Therapeutic Target for Parkinson’s Disease?
Luo, Y., Hoffer, A., Hoffer, B. J., & Qi, X. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160920704 · Cited by 108
Inhibition of mitochondrial fission favours mutant over wild-type mitochondrial DNA
Malena, A., Loro, E., Di Re, M., Holt, I. J., & Vergani, L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp281 · Cited by 107
Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction
Martín‐Montalvo, A., & de Cabo, R. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4866 · Cited by 106
Increased mitochondrial biogenesis in muscle improves aging phenotypes in the mtDNA mutator mouse
Dillon, L. M., Williams, S. L., Hida, A., Peacock, J. D., Prolla, T. A., Lincoln, J., & Moraes, C. T. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds049 · Cited by 102
Autophagy and Protein Turnover Signaling in Slow-Twitch Muscle during Exercise
PAGANO, A. F., PY, G., BERNARDI, H., CANDAU, R. B., & SANCHEZ, A. M. J. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000237 · Cited by 96
Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication
Holmes, J. B., Akman, G., Wood, S., Sakhuja, K., Cerritelli, S. M., Moss, C. F., Bowmaker, M., Jacobs, H. T., Crouch, R. J., & Holt, I. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1503653112 · Cited by 93
DNA polymerases and human diseases
Sweasy, J. B., Lauper, J. M., & Eckert, K. A. (2006) · Radiation Research · doi:10.1667/rr0706.1 · Cited by 93
A Novel Polymerase γ Mutation in a Family With Ophthalmoplegia, Neuropathy, and Parkinsonism
Mancuso, M., Filosto, M., Oh, S. J., & DiMauro, S. (2004) · Archives of Neurology · doi:10.1001/archneur.61.11.1777 · Cited by 92
Selective autophagy in the maintenance of cellular homeostasis in aging organisms
Hubbard, V. M., Valdor, R., Macián, F., & Cuervo, A. M. (2011) · Biogerontology · doi:10.1007/s10522-011-9331-x · Cited by 90
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Metadata
- Authors
- DeBalsi, K. L., Hoff, K. E., & Copeland, W. C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Copeland, William C.
- ORCID
- Copeland, William C.
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 33
- Pages
- 89-104
- ISSN
- 1568-1637 (ISSN-L)
- PMC
- PMC5086445
- OpenAlex
- W2344148285
- Semantic Scholar
- 8003ba7a002a2d21b3e89efa176e72ca5094b243
- Cited by
- 180
- References
- 276
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 13 · 2022: 24 · 2021: 31 · 2020: 29 · 2019: 14 · 2018: 18 · 2017: 14
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (Z01ES065078)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial DNA replication, mitochondrial dysfunction, aging, age-related diseases, reactive oxygen species, clonal expansion, mitochondrial dynamics, electron transport chain, cellular respiration
- MeSH terms
- Aging, DNA Replication, DNA, Mitochondrial, Humans, Mitochondria, Mutation, Mutagenesis, Reactive Oxygen Species, Genes, Mitochondrial
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