Investigation of the signaling pathways involved in the proliferative life span barriers in werner syndrome fibroblasts

Annals of the New York Academy of Sciences
Terence DavisDavid Kipling

Abstract

Werner syndrome (WS) fibroblasts enter replicative senescence after a reduced in vitro life span. Although this has been postulated as causal in the accelerated aging seen in this disease, controversy remains as to whether WS is showing the acceleration of a normal cellular aging mechanism or, instead, the occurrence of a novel WS-specific process. To address this, we analyzed the signaling pathways involved in senescence in WS fibroblasts. Cultured WS fibroblasts underwent senescence after approximately 20 population doublings, with the majority of the cells having a 2N DNA content. This was associated with high levels of the CdkIs p16 and p21. Senescent WS cells reentered the cell cycle after microinjection of a p53-neutralizing antibody. Similarly, presenescent WS fibroblasts expressing the E6 and/or E7 oncoproteins bypassed M1 and ultimately reached a second proliferative life span barrier, which strongly resembled the second life span barriers found in normal cells for growth dynamics, cellular morphology, and expression of p16 and p21. The strong similarity between the signaling pathways triggering cell cycle arrest in WS and normal fibroblasts provides support for the defect in WS causing the acceleration of a normal agi...Continue Reading

References

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Sep 14, 1999·Journal of the American Geriatrics Society·G M MartinM Poot
Jun 29, 2002·Nature Biotechnology·Woodring E Wright, Jerry W Shay
Jul 29, 2003·Aging Cell·Ana M Rodríguez-LópezLynne S Cox

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Citations

Dec 13, 2005·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Terence DavisDavid Kipling
Jun 4, 2010·Pharmaceuticals·Mark C BagleyDavid Kipling
Jun 29, 2006·Annals of the New York Academy of Sciences·Terence DavisDavid Kipling
Jan 25, 2005·Experimental Gerontology·Terence DavisDavid Kipling
Dec 21, 2013·International Journal of Molecular Medicine·Masanobu Sugimoto

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