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.

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