X-Message-Number: 25716 Date: Wed, 23 Feb 2005 05:17:43 -0800 (PST) From: Doug Skrecky <> Subject: could SIPS be responsible for aging? Biochem Pharmacol. 2002 Sep;64(5-6):1007-9. Stress-induced premature senescence and tissue ageing. Various human proliferative cell types exposed in vitro to many types of subcytotoxic stresses undergo stress-induced premature senescence (SIPS). The known mechanisms of appearance the main features of SIPS are reviewed: senescent-like morphology, growth arrest, senescence-related changes in gene expression. All cell types undergoing SIPS in vivo, are likely to participate in the tissular changes observed along ageing. For instance, human diploid fibroblasts exposed in vivo and in vitro to pro-inflammatory cytokines display biomarkers of senescence and might participate in the degradation of the extracellular matrix observed in ageing. [Although proteasome inhibition can induce some aspects of senescence, the following article implies that proteasome inhibition is not responsible for SIPS induced senescence.] J Cell Sci. 2005 Feb 15;118(Pt 4):743-58. Epub 2005 Jan 25. Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-{beta}1 signaling pathway. Premature senescence of human diploid fibroblasts (HDFs) can be induced by exposures to a variety of oxidative stress and DNA damaging agents. In this study we developed a robust model of UVB-induced premature senescence of skin HDFs. After a series of 10 subcytotoxic (non-proapoptotic) exposures to UVB at 250 mJ/cm(2), the so-called biomarkers of senescence were markedly expressed: growth arrest, senescence-associated beta-galactosidase activity, senescence-associated gene overexpression, deletion in mitochondrial DNA. A set of 44 stress- and senescence-associated genes were found to be differentially expressed in this model, among which clusterin/apolipoprotein J (apo J) and transforming growth factor-beta1 (TGF-beta1). Transfection of apo J cDNA provided protection against premature senescence-inducing doses of UVB and other stressful agents. Neutralizing antibodies against TGF-beta1 or its receptor II (TbetaRII) sharply attenuated the senescence-associated features, suggesting a role for TGF-beta1 in UVB-induced premature senescence. Both the latent and active forms of TGF-beta1 were increased with time after the last UVB stress. Proteasome inhibition was ruled out as a potential mechanism of UVB-induced stress-induced premature senescence (SIPS). This model represents an alternative in vitro model in photoaging research for screening potential anti-photoaging compounds. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=25716