I thought this might be interesting if not previously posted, suggesting a further relationship between telomeres shrinking and "programmed" epigenetic changes.
I don't know how much of the article am I allowed to post, I'll try to make some quotations..
and moreUsing telomerase-deficient TRF2-overexpressing mice (K5TRF2/Terc/) as a model for accelerated aging, we show that telomere shortening is paralleled by a gradual deregulation of the mammalian transcriptome leading to cumulative changes in a defined set of genes, including up-regulation of the mTOR and Akt survival pathways and down-regulation of cell cycle and DNA repair pathways.
[..]
Collectively, these findings suggest that critically short telomeres activate a persistent DNA damage response that alters gene expression programs in a nonstochastic manner toward cell cycle arrest and activation of survival pathways, as well as impacts the maintenance of epigenetic memory and nuclear organization, thereby contributing to organismal aging.
Interestingly, epigenetic alterations at heterochromatic regions [telomeres] are proposed to lead to changes in gene expression associated with aging (14–16).
[..]
An important question to determine ishowthe various types of DNA damage impact gene expression changes associated with organismal aging.
[..]
In this study, we focused on the isolated effect of dysfunctional telomeres on global genome regulation. Using a mouse model system, we provide evidence that progressive telomere shortening in stratified epithelia, such as the skin, is linked to global deregulation of the mammalian transcriptome and loss of maintenance of epigenetic silencing mechanisms.
source:
Nature Reviews. Genetics, DECEMBER 2009 VOL 10 NO 12
original article:
Schoeftner, S. et al. Telomere shortening relaxes X chromosome
inactivation and forces global transcriptome alterations. Proc. Natl Acad. Sci. USA 3 Nov 2009
(doi:10.1073/pnas.0909265106)
