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.
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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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“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.
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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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
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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
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Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060
Cited by
Sorted by citations
Items 101–181 of 181
Dysfunction of the neurovascular unit in brain aging
Liu, S., Xu, Y., Chen, F., & Cai, Z. (2023) · Journal of Biomedical Research · doi:10.7555/jbr.36.20220105 · Cited by 14
Shi, Y., Tong, X., Weng, Y., Xiao, Y., Wu, J., Wang, J., Wang, W., Yan, M., Yan, M., Li, Z., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05953-7 · Cited by 12
Structural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase
Li, Z., Kaur, P., Lo, C., Chopra, N., Smith, J., Wang, H., & Gao, Y. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1089 · Cited by 12
“Mutations and deletions in the mitochondrial genome are correlated with numerous neuromuscular diseases and premature aging (9).”
BackgroundAging through the lens of mitochondrial DNA mutations and inheritance paradoxes
Chen, J., Li, H., Liang, R., Huang, Y., & Tang, Q. (2024) · Biogerontology · doi:10.1007/s10522-024-10175-x · Cited by 12
“Such impairments reduce the efficiency of electron transport, leading to decreased ATP synthesis and, consequently, a decline in cellular energy levels (DeBalsi et al. 2017).”
Microvesicles carrying EV71 virions cross BBB through endocytic pathway to induce brain injury
Tian, X., Liu, B., Li, L., Yuan, M., You, Q., Zhang, R., Chen, D., Cheng, M., Zheng, N., He, M., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02195-y · Cited by 14
“As being a critical subcellular structure for normal cellular and organismal function [34, 35], mitochondria dysfunction can cause a number of human diseases, such as Parkinson’s disease and Alzheimer’s disease [36].”
The Relationship between Mitochondria and Neurodegeration in the Eye: A Review
Liu, H., Liu, H., & Prokosch, V. (2021) · Applied Sciences · doi:10.3390/app11167385 · Cited by 11
“Mitochondrial dysfunction and altered mitochondrial dynamics are some of the main causes of aging and age‐related diseases [42].”
BackgroundLi, X., Zhang, Y., Yu, J., Mu, R., Wu, L., Shi, J., Gong, L., & Liu, D. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.6290 · Cited by 11
“Mitochondria are dynamic organelles, which are continuously remodeled through the dynamic processes, including fusion, fission and mitophagy (1).”
Park, J., Herrmann, G. K., Roy, A., Shumate, C. K., Cisneros, G. A., & Yin, Y. W. (2024) · Science Advances · doi:10.1126/sciadv.adl3214 · Cited by 10
“Mutations in Pol γ have been implicated in neurological and muscular disorders, and exo-deficient variants lead to premature aging [see review ( 4 )].”
BackgroundVallabh, N. A., Lane, B. S., Simpson, D. A. C., Fuchs, M., Choudhary, A., Criddle, D. N., Cheeseman, R., & Willoughby, C. E. (2024) · Scientific Reports · doi:10.1038/s41598-024-72684-6 · Cited by 11
“Oxidative damage to mtDNA usually results in G: C and T: A transversion mutations 52,57 and the majority of mtDNA variants in our data were transitions.”
Schniertshauer, D., Wespel, S. L., & Bergemann, J. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45050250 · Cited by 11
Building the case for mitochondrial transplantation as an anti-aging cardiovascular therapy
Headley, C. A., & Tsao, P. S. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1141124 · Cited by 11
“Interestingly, hTFAM is incapable of initializing murine mtDNA synthesis (80).”
BackgroundMethodInfluentialPolypharmacy and sun exposure: Implications for mitochondrial DNA deletions in skin
Powers, J. M., MURPHY, G. M., Ralph, N., O’Gorman, S. M., & Murphy, J. E. (2017) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2017.06.020 · Cited by 10
The hidden driver of osteoporosis: mitochondria-dominated inflammation
Yan, B., Ju, W., Xue, H., Xu, Z., Qiu, D., & Tan, G. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02453-z · Cited by 12
“Specifically, mtDNA mutations and impaired repair accumulate with age, leading to electron transport chain dysfunction and reduced energy production efficiency [189].”
Torres, A. S., Lee, J.-E., Caporali, A., Semple, R. K., Horrocks, M. H., & MacRae, V. E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252010973 · Cited by 9
“Additionally, research suggests that the mitochondrial DNA repair system may be less efficient than that of nuclear DNA, and mtDNA lacks the protective histone proteins, rendering it more susceptible to harmful agents [148].”
BackgroundGarcía‐Olivares, V., Muñoz‐Barrera, A., Lorenzo-Salazar, J. M., Zaragoza‐Trello, C., Rubio‐Rodríguez, L. A., Usera, A. D.-D., Jáspez, D., Íñigo-Campos, A., González‐Montelongo, R., & Flores, C. (2021) · Scientific Reports · doi:10.1038/s41598-021-99895-5 · Cited by 9
Peralta-Castro, A., García‐Medel, P. L., Baruch‐Torres, N., Trasviña‐Arenas, C. H., Juárez-Quintero, V., Morales‐Vázquez, C. M., & Brieba, L. G. (2020) · Genes · doi:10.3390/genes11111370 · Cited by 8
“In humans, errors in mitochondrial DNA replication are associated with aging and a plethora of diseases [38].”
BackgroundCha, J. H., Lee, S., Yun, Y., Choi, W. H., Koo, H., Jung, S. H., Chae, H. B., Lee, S. J., Lee, S. J., Jo, D. H., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102257 · Cited by 7
Increase of mtDNA number and its mutant copies in rat brain after exposure to 150 MeV protons
Abdullaev, S. A., Bulanova, T., Тимошенко, Г. Н., & Gaziev, A. I. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05491-7 · Cited by 11
“Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?
Mietsch, M., & Hinkel, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041824 · Cited by 9
“Recent studies showed the accumulation of spontaneous mutations to likely be the main reason for these increases [80].”
BackgroundMitochondrial DNA-dependent inflammation in kidney diseases
Luo, S., Yang, M., Zhao, H., Han, Y., Liu, Y., Xiong, X., Chen, W., Li, C., & Sun, L. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108637 · Cited by 7
Polymerase ζ Is Involved in Mitochondrial DNA Maintenance Processes in Concert with APE1 Activity
Schreier, H. K., Wiehe, R. S., Ricchetti, M., & Wiesmüller, L. (2022) · Genes · doi:10.3390/genes13050879 · Cited by 7
“As a positive control, we examined the localization of POLGA adjacent to TFAM, both well described mitochondrial matrix proteins [6,64], and found formation of distinct PLA foci, as expected (Figure 7b).”
BackgroundRueda, M., & Torkamani, A. (2017) · BMC Bioinformatics · doi:10.1186/s12859-017-1778-6 · Cited by 8
Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
Panov, A. V., Dikalov, S., Darenskaya, M. A., et al. (2020) · Бюллетень Восточно-Сибирского научного центра Сибирского отделения Российской академии медицинских наук · doi:10.29413/abs.2020-5.4.5 · Cited by 7
Wang, P., Wu, B., You, S., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.65030 · Cited by 6
“Especially various mutation of PolG affected mitochondrial quality control processes, leading to abnormal accumulation of defective mtDNA and mitochondrial dysfunction [2, 7-11].”
BackgroundTelomere length and mitochondrial DNA copy number in bipolar disorder: A sibling study
Spano, L., Étain, B., Laplanche, J., Leboyer, M., Gard, S., Bellivier, F., & Cynthia Marie-claire, A. (2022) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2022.2131907 · Cited by 7
“A decrease of mtDNAcn has also been associated with age as a result of an accumulation of mutations and damages (Ashar et al. 2015; DeBalsi et al. 2017).”
BackgroundUpdates on the Pivotal Roles of Mitochondria in Urothelial Carcinoma
Huang, C.-C., Liu, H., Hsu, T., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10102453 · Cited by 5
Mitochondrial genome and risk of multiple sclerosis
Boyko, A. N., Kozin, M. S., Осьмак, Г. Ж., Кулакова, О. Г., & Favorova, O. O. (2019) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2019-3-43-46 · Cited by 5
Tang, L., Yang, S., Wang, H., Gu, H., Xia, X., Feng, Y., Yang, Z., Zhao, S., Su, C., Su, Z., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.23243 · Cited by 5
“Previous work has revealed the increased oxidative stress condition and intracellular ROS levels in chronically HIV1-infected patients [23]; these changes adversely affected the stability of the intracellular environment for the cells of AIDS patients and aggravated the disease progression [9].”
BackgroundMethodYurdgülü, E. E., Ay, Y. A., Bayır, Y., & Halıcı, Z. (2026) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2026.106990 · Cited by 4
Chronic Inflammation and Aging (Inflammaging)
Tan, B. L., & Norhaizan, M. E. (2021) · Springer eBooks · doi:10.1007/978-3-030-82859-2_4 · Cited by 4
Musci, R. V., Fuqua, J. D., Peelor, F. F., Nguyen, H. V. M., Richardson, A. G., Choi, S., Miller, B. F., & Wanagat, J. (2024) · GeroScience · doi:10.1007/s11357-024-01344-4 · Cited by 5
“Similar to the nuclear genome, age-induced changes in mitochondrial genome integrity include copy number variation, nucleotide damage, and mutations [7–10] that are linked to numerous age-related diseases [11–15].”
Rojas, V., Carrasco‐Gallardo, C., Tenorio, L., Olesen, M. A., Tapia, V., Carrasco, M., Araos, P. A., Quintanilla, R. A., & Ruíz, L. M. (2024) · Autism Research · doi:10.1002/aur.3277 · Cited by 4
“However, excessive or uncontrolled mtDNA replication can lead to problems, including the accumulation of mutated mtDNA copies (DeBalsi et al., 2017).”
Metabolic Syndrome as the First Stage of Eldership; the Beginning of Real Aging
Panov, A. V., Darenskaya, M. A., Dikalov, S., & Kolesnikov, S. I. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.95464 · Cited by 7
Irvin, E. M., & Wang, H. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103528 · Cited by 4
Liang, C., Zhou, X., Li, M., Song, Z., & Lan, J. (2022) · BioMed Research International · doi:10.1155/2022/3529499 · Cited by 4
“In the process of apoptosis, the Bcl-2 protein family plays an important role [37, 38].”
BackgroundRetractedDeveloping mitochondrial DNA field-compatible tests
Dhar, B. C., Roche, C. E., & Levine, J. F. (2021) · Critical Reviews in Environmental Science and Technology · doi:10.1080/10643389.2021.1904709 · Cited by 5
“Transcription, replication, and repair of mtDNA is dependent on cell nuclear DNA (Capps et al., 2003; DeBalsi et al., 2017; Scheibye-Knudsen et al., 2015).”
BackgroundDieter, F., Jacobs, K., Quentin, A., Prvulovic, D., Reif, A., Pantel, J., Pilatus, U., Hattingen, E., Matura, S., & Eckert, G. P. (2025) · GeroScience · doi:10.1007/s11357-025-01813-4 · Cited by 5
“Factors such as mitochondrial DNA replication [5, 6], the generation of reactive oxygen species (ROS) [7] and impaired oxidative phosphorylation [8–10] contribute significantly to age-related mitochondrial dysfunction, ultimately leading to reduced ATP production [9].”
Sommers, J. A., Estep, K. N., Maul, R. W., & Brosh, R. M. (2021) · Methods · doi:10.1016/j.ymeth.2021.12.005 · Cited by 3
Choroby mitochondrialne, postęp w badaniu i leczeniu
Bartnik, E., Tońska, K., & Rusecka, J. M. (2018) · Postępy Biochemii · doi:10.18388/pb.2018_143 · Cited by 3
Rygiel, K. A., Dodds, R. M., Patel, H. P., Syddall, H. E., Westbury, L. D., Granic, A., Cooper, C. C., Cliff, J., Rocha, M. C., Turnbull, D. M., et al. (2017) · JCSM Clinical Reports · doi:10.17987/jcsm-cr.v2i2.35 · Cited by 3
“The heterogeneity of an individual person’s mitochondria is also thought to increase with age [36] and this effect could have contributed to the within‐participant variance that we observed.”
BackgroundEvaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities
Zussman, J. W., Skinner, D. J., Wagner, D. E., Shvartsman, S. Y., & Laird, D. J. (2025) · Annual Review of Genetics · doi:10.1146/annurev-genet-021925-093551 · Cited by 4
Bosanac, M., Andrejić-Višnjić, B., Popović, A., Ljubković, M., Martić, N., Miljković, D., Stupar, A., & Cvetković, B. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18060662 · Cited by 2
Singh, L., & Singh, M. K. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.96368 · Cited by 3
“A catalytic subunit and an accessory subunit consist of a nuclear-encoded Pol-γ holo-enzyme [40].”
BackgroundInfluentialLiu, A., Wei, Q., Lin, H., Ding, Y., Sun, Y. V., Zhao, D., He, J., Ma, Z., Li, F., Zhou, S., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.793375 · Cited by 2
“Growing evidence shows that CD4+T-cell loss-related noncommunicable chronic diseases (NCDs) emerge as pervasive health concerns in HIVinfected populations (28–30) and expansion of mitochondrial DNA mutations linked to increased apoptosis drives aging and age-related diseases (31, 32).”
BackgroundLi, Z., Lin, H.-S., Huang, X.-P., Zhang, S.-Q. Y., Shu, X., & Wu, X. (2023) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2023.04 · Cited by 2
Mitochondrial Function in Aging
Morales-Rosales, S. L., Rivero-Segura, N. A., & Königsberg, M. (2020) · Springer eBooks · doi:10.1007/978-3-030-40955-5_4 · Cited by 3
Mitochondrial DNA Maintenance Disorders: Impact of Impaired Deoxynucleoside Triphosphates Metabolism
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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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