2015
DOI: 10.1101/cshperspect.a025130
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Abstract: Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage ma… Show more

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Cited by 284 publications
(177 citation statements)
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References 168 publications
(200 reference statements)
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“…Progressive damage to nuclear DNA and mitochondrial DNA (mtDNA) is considered to be a prominent contributing factor to the ageing process and may underlie several age-associated diseases 4,20,28,29 . Cells have multiple DNA repair pathways to rectify the myriad types of DNA lesions that occur and to maintain DNA integrity in the nucleus and in mitochondria (BOX 1).…”
Section: Nuclear Dna Repair and Mitochondrial Healthmentioning
confidence: 99%
See 1 more Smart Citation
“…Progressive damage to nuclear DNA and mitochondrial DNA (mtDNA) is considered to be a prominent contributing factor to the ageing process and may underlie several age-associated diseases 4,20,28,29 . Cells have multiple DNA repair pathways to rectify the myriad types of DNA lesions that occur and to maintain DNA integrity in the nucleus and in mitochondria (BOX 1).…”
Section: Nuclear Dna Repair and Mitochondrial Healthmentioning
confidence: 99%
“…As DNA is constantly assaulted by both endogenous (for example, reactive oxygen species and hydrolysis) and exogenous (such as ultraviolet and ionizing radiation) stresses, cells have evolved several DNA repair pathways to maintain the integrity of DNA 3,4,141144 . Major DNA repair pathways in the nucleus include direct reversal (DR) of the lesion (usually methylation), base excision repair (BER), mismatch repair (MMR), nucleotide excision repair (NER; comprising global genome NER and transcription-coupled NER), double-strand break repair (DSBR, which includes non-homologous end-joining (NHEJ) and homologous recombination (HR)) and inter-strand crosslink repair (ICLR), among others (see the figure).…”
Section: Nuclear Dna Repair and Mitochondrial Healthmentioning
confidence: 99%
“…Just like CIN can cause DNA damage that is regarded as a main cause of GIN, it is often difficult to dissect causes and consequences of various forms of GIN. Accumulation of GIN, both at the nucleotide (Maynard et al, 2015) and chromosome level (Ricke and van Deursen, 2013; Yurov et al, 2014), is associated with neurodegenerative diseases (ND). Below we summarize succinctly the main types of GIN, how they are generated, their known correlation with CIN, and how they relate to aging and ND.…”
Section: Gin-cin Complexity: a Two Sided Coinmentioning
confidence: 99%
“…DNA damage is known to be associated with neurodegeneration 132,133 , making this mechanism a prime candidate. Furthermore, oxidative stress and mitochondrial dysfunction are known to occur in FXTAS 70,71,134,135 and would increase the likelihood of DNA damage.…”
Section: Molecular Pathogenesis Of Fxtasmentioning
confidence: 99%