Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of Ataxia Telangiectasia and Werner syndrome fibroblasts

Davis, Terence ORCID: https://orcid.org/0000-0003-2780-0262 and Kipling, David Glyn 2009. Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of Ataxia Telangiectasia and Werner syndrome fibroblasts. Biogerontology 10 (3) , pp. 253-266. 10.1007/s10522-008-9179-x

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Abstract

The premature ageing Ataxia Telangiectasia (AT) and Werner syndromes (WS) are associated with accelerated cellular ageing. Young WS fibroblasts have an aged appearance and activated p38 MAP kinase, and treatment with the p38 inhibitor SB230580 extends their lifespan to within the normal range. SB203580 also extends the replicative lifespan of normal adult dermal fibroblasts, however, the effect is much reduced when compared to WS cells, suggesting that WS fibroblasts undergo a form of stress-induced premature senescence (SIPS). A small lifespan extension is seen in AT cells, which is not significant compared to normal fibroblasts, and the majority of young AT cells do not have an aged appearance and lack p38 activation, suggesting that the premature ageing does not result from SIPS. The lack of p38 activation is supported by the clinical manifestation, since AT is not associated with inflammatory disease, whereas WS individuals are predisposed to atherosclerosis, type II diabetes and osteoporosis, conditions known to be associated with p38 activation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	c-Jun; HSP27; Inflammatory disease; JNK; Premature ageing; SB203580; Stress-induced premature senescence; Therapeutics
Additional Information:	From the issue entitled "Special issue on Cellular Senescence"
Publisher:	Springer
ISSN:	1389-5729
Last Modified:	08 May 2023 17:47
URI:	https://orca.cardiff.ac.uk/id/eprint/23233

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