Absence of premature senescence in Werner's syndrome keratinocytes

Ibrahim, Badr and Sheerin, Angela and Jennert-Burston, Katrin and Bird, Joseph and Massala, M and Illsley, Matthew and James, Elizabeth and Faragher, Richard (2016) Absence of premature senescence in Werner's syndrome keratinocytes. Experimental gerontology, 83. pp. 139-147. ISSN 0531-5565

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Official URL: http://dx.doi.org/10.1016/j.exger.2016.07.017

Abstract

Werner's syndrome (WS) is an autosomal recessive genetic disorder caused by loss of function mutation in wrn and is a useful model of premature in vivo ageing. Cellular senescence is a plausible causal mechanism of mammalian ageing and, at the cellular level,WS fibroblasts showpremature senescence resulting froma combination of telomeric attrition and replication fork stalling. Over 90% of WS fibroblast cultures achieve b20 population doublings (PD) in vitro compared to wild type human fibroblast cultures. It has been proposed that some cell types, capable of proliferation, will fail to show a premature senescence phenotype in response to wrn mutations. To test this hypothesis, human dermal keratinocytes (derived from both WS and wild type patients) were cultured long term. WS Keratinocytes showed a replicative lifespan in excess of 100 population doublings but maintained functional growth arrest mechanisms based on p16 and p53. The karyotype of the cells was superficially normal and the cultures retained markers characteristic of keratinocyte holoclones (stem cells) including p63 expression and telomerase activity. Accordingly we conclude that, in contrast to WS fibroblasts, WS keratinocytes do not demonstrate slow growth rates or features of premature senescence. These findings suggest that the epidermis is among the tissue types that do not display symptoms of premature ageing caused by loss of function of wrn. This is in support that Werner's syndrome is a segmental progeroid syndrome.

Item Type: Journal Article
Additional Information: http://eprints.brighton.ac.uk/16053/
Keywords: Werner's syndrome, Keratinocytes, Cellular senescence, Ageing, p53, p63, Fibroblasts
Faculty: Faculty of Science & Technology
Depositing User: Unnamed user with email Joseph.Bird@anglia.ac.uk
Date Deposited: 10 Mar 2017 15:39
Last Modified: 10 Mar 2017 15:39
URI: http://arro.anglia.ac.uk/id/eprint/701563

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