2015
DOI: 10.18632/aging.100723
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Abstract: Dermal fibroblasts provide a paradigmatic model of cellular adaptation to long-term exogenous stress and ageing processes driven thereby. Here we addressed whether fibroblast ageing analysed ex vivo entails genome instability. Dermal fibroblasts from human female donors aged 20–67 years were studied in primary culture at low population doubling. Under these conditions, the incidence of replicative senescence and rates of age-correlated telomere shortening were insignificant. Genome-wide gene expression analysi… Show more

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Cited by 29 publications
(25 citation statements)
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References 56 publications
(89 reference statements)
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“…27,28 Although the previous work greatly advanced our understanding of age-associated changes of DNA DSB repair, due to a lack of proper tools for the analysis of NHEJ and HR efficiency and fidelity separately, and the hardship of acquiring a sufficient number of human samples, whether NHEJ efficiency and fidelity, and HR efficiency change with age in humans and the consequences of any such change, and its underlying molecular mechanism are not well understood. Here, we established 50 eyelids fibroblast cell lines derived from donors who are evenly distributed by age.…”
Section: Discussionmentioning
confidence: 99%
“…This can be also correlated to well-documented clinical differences in wound healing. Similarly, the number of DNA strand breaks and time required for their repair is significantly influenced by ageing (22,23). Double-strand DNA breaks can even participate to the loss of heterozygosity in the elderly and can be important for cancerogenesis (24,25).…”
Section: Biological Background Of Ageing and Impact On Cancer Formationmentioning
confidence: 99%
“…As a consequence, mammalian cell-based alternatives to typical animal-based clastogenicity assays are needed for early screening of mammalian genotoxicity (65). The automated FADU assay is a cell-based in vitro system, which is well suited for the measurement of DNA strand breaks in different types of human cell lines (125,126), as well as in primary human cells such as PBMCs, lymphocytes (126129) and/or fibroblast (130) obtained from different subjects. The automated FADU offers an alternative method for reducing animal use during genotoxicity risk assessments.…”
Section: Modifications Of the Automated Fadu Assaymentioning
confidence: 99%
“…With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 .…”
mentioning
confidence: 99%
“…Mutations accumulate in aging skin as in all other mammalian tissues (4). Primary FBs from breast skin of donors aged 20-70 showed exponential increases in double-strand DNA breaks (histone marker ϒH2AX) against a linear doubling of chromosome structural abnormalities, 10% to 20% across the adult lifespan (5). Are their corrective mechanisms as part of the reprogramming process, and if so, how do these work?…”
mentioning
confidence: 99%