X-Message-Number: 25672
Date: Mon, 7 Feb 2005 18:55:11 -0800 (PST)
From: Doug Skrecky <>
Subject: are stem cell defects driving aging?

Annu Rev Med. 2005 Feb 18;56:495-508
DNA REPAIR DEFECTS IN STEM CELL FUNCTION AND AGING *
  Cellular DNA is under constant challenge by exogenous and endogenous
genotoxic stress, which results in both transient and accumulated DNA
damage and genomic instability. All cells are equipped with DNA damage
response pathways that trigger DNA repair, cell cycle arrest, and, if
need be, apoptosis, to eliminate DNA damage or damaged cells. The
consequences of these processes for stem cells can be profound:
diminution in stem cell pools, or, because of altered gene expression, an
increased chance for stem cell differentiation or malignant
transformation. Furthermore, a number of DNA repair abnormalities are
linked to premature aging syndromes, and these are associated with
defects in the stem cell population. The specific DNA repair systems for
which there are data regarding the impact of repair defects on stem cell
function include O(6)-alkylguanine DNA alkyltransferase, nucleotide
excision repair, base excision repair, mismatch repair, non-homologous
DNA end-joining Fanconi's anemia protein complex, and homologous
recombination. It has recently become clear that deficiencies of these
processes are associated not only with cancer and/or aging but also with
stem cell defects. This discovery raises the possibility of a link between
aging and stem cell dysfunction. In this review, we provide evidence for
a link between DNA repair systems and the maintenance and longevity of
stem cells.

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