tmatth at netcom.ca
Mon Aug 31 18:31:38 EST 1998
T.D. Laing wrote:
> Senescent cells appear to express more matrix metalloproteinases than
> younger cells, and respond differently to TGF-beta (from Medline):
I just want to note that your use of the term "senescent" here is not
"technically" correct. The technical meaing of "senescent cells" is
cells which are no longer able to divide. The abstract which you posted
is most interesting, but it contrasts younger cells with older cells
which are not necessarily senescent.
> Exp Gerontol 1996 Jan;31(1-2):207-223
> Differential effects of transforming growth factor-beta 1 on the
> expression of matrix metalloproteinases and tissue inhibitors of
> metalloproteinases in young and old human fibroblasts.
> Edwards DR, Leco KJ, Beaudry PP, Atadja PW, Veillette C, Riabowol KT
> Department of Pharmacology and Therapeutics, University of Calgary,
> Alberta, Canada.
> The balance between the activities of matrix metalloproteinases (MMPs) and
the tissue inhibitors of metalloproteinases (TIMPs) is an important
point in tissue remodeling. Previous studies have demonstrated elevated
expression of the MMPs collagenase and stromelysin-1 by aged human
fibroblasts compared to early-passage cultures. We show here that aging
cells display an altered response to transforming growth factor-beta 1
beta 1) that selectively affects MMP mRNA expression. In both young and
old cells, phorbol myristoyl-13 acetate (PMA) induced the expression of
transcripts of collagenase, stromelysin-1, gelatinase-B, TIMP-1, and
TIMP-3. In young cells, TGF beta 1 reciprocally modulated PMA-induced
and TIMP gene expression leading to reduced levels of transcripts for
MMPs and augmented accumulation of TIMP-1 and TIMP-3 mRNAs.
However, repressing effects of TGF beta 1 on collagenase,
and gelatinase-B RNA expression were not apparent in old cells, though
induction of the TIMP genes was unimpaired. By electrophoretic mobility
shift analysis the nuclear transcription factors AP1 and serum response
(SRF) showed reduced levels of DNA binding activities in old
compared to young cells. A probe for the TGF beta-inhibitory element
gave equivalent levels of complexes with nuclear extracts from both
of cells, though of different mobilities. We conclude that the effects
TGF beta 1 on MMP and TIMP gene expression involve different cellular
intermediaries, and suggest that altered composition or modification of
TIE binding factors in aging cells may underlie the failure of TGF beta
1-mediated transcription repression. This mechanism may contribute to
expression of MMPs in old cells and to the connective tissue
> that accompanies the aging process.
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