Stress‐induced Premature Senescence (SIPS)

Olivier Toussaint, University of Namur, Namur, Belgium
Michel Salmon, University of Namur, Namur, Belgium
Thierry Pascal, University of Namur, Namur, Belgium
Joao Pedro Magalhaes, University of Namur, Namur, Belgium
Florence Chainiaux, University of Namur, Namur, Belgium

Published online: May 2005

DOI: 10.1038/npg.els.0003865

Replicative senescence is a process in which normal proliferative cells lose replicative potential and acquire specific biomarkers as a result of serial passages in culture. Stress-induced premature senescence (SIPS) is the long-term appearance of the biomarkers of replicative senescence after exposure of human diploid cells to subcytotoxic stress. The processes of signal transduction triggering SIPS are now better understood, as well as the changes in protein expression taking place in SIPS. SIPS could play a role in the tissue changes occurring with in vivo ageing, as biomarkers of replicative senescence also appear after repeated exposure of human diploid fibroblasts not only to various types of oxidative stress but also to proinflammatory cytokines.

Keywords: stress-induced premature senescence; oxidative stress; fibroblasts; cytokines; toxicology; signal transduction; proteomics

Figure 1. DNA damage can induce and/or activate p53, which acts as a transcription factor to induce cyclin-dependent kinase inhibitor (CdkI) p21waf-1 expression. p21waf-1 inhibits the kinase activity (phosphorylation activity) of the Cyclin D1–Cdk complexes, which are no longer able to phosphorylate the retinoblastoma protein pRB. p16ink-4 inhibits the kinase activity of the cyclin E–Cdk complexes. When hypophosphorylated, the pRB forms a complex with E2F transcription factors. When complexed with pRB, E2F cannot induce the transcription of genes necessary for the cells to start the S phase of the cell cycle, such as the genes of dihydrofolate reductase (DHFR) and thymidine kinase (TK).
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 Further Reading
    Brack C, Lithgow GJ, Osiewacz H and Toussaint O (2000) Molecular and cellular gerontology. EMBO Journal 19: 1929–1934.
    book Campisi J (1999) "Replicative senescence and immortalization". In: Stein GS, Baserga R, Giordano A and Denhardt DT (eds) The Molecular Basis of Cell Cycle and Growth Control, pp. 348–373. New York: Wiley-Liss.
    Chainiaux F, Magalhaes JP, Eliaers F, Remacle J and Toussaint O (2002) UV-B induced premature senescence of human diploid skin fibroblasts. International Journal of Biochemistry and Cell Biology 34: 1331–1339.
    Dierick J-F, Kalume D, Wenders F et al. (2002) Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence. FEBS Letters 531: 499–504.
    Dumont P, Chen QM, Burton M et al. (2000) Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast. Free Radicals in Biology and Medicine 28: 361–373.
    Frippiat C, Chen QM, Zdanov S et al. (2001) Subcytotoxic  H2O2 stress triggers a release of transforming growth factor-1, which induces stress-induced premature senescence of human diploid fibroblasts. Journal of Biological Chemistry 276: 2531–2537.
    Frippiat C, Dewelle J, Remacle J and Toussaint O (2002) Signal transduction in  H2O2-induced senescence-like phenotype in human diploid fibroblasts. Free Radicals in Biology and Medicine 33: 1334–1346.
    Magalhaes JP, Chainiaux F, Remacle J and Toussaint O (2002) Stress-induced premature senescence in BJ and hTERT-BJI human diploid fibroblasts. FEBS Letters 523: 157–162.
    Toussaint O, Dumont P, Dierick J-F et al. (2002) Hayflick mosaic or stress-induced premature senescence? Is it stress-induced premature senescence or replicative senescence that occurs in vivo? International Journal of Biochemistry and Cell Biology 34: 1415–1429.
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Related Sub-Topics:

Cell Death and Cellular Senescence | Chromosomes and Chromatin Modifications | DNA Damage and Repair | Mechanisms of Cell Death, Senescence and Metabolism
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Article Title: Stress‐induced Premature Senescence (SIPS)
 
How to Cite close
Toussaint, Olivier, Salmon, Michel, Pascal, Thierry, Magalhaes, Joao Pedro, and Chainiaux, Florence(May 2005) Stress‐induced Premature Senescence (SIPS). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003865]