X-Message-Number: 25587
Date: Wed, 19 Jan 2005 20:17:17 -0800 (PST)
From: Doug Skrecky <>
Subject: telomere shortening with age

[Stable telomeres in liver after middle age?]

J Gerontol A Biol Sci Med Sci. 2000 Nov;55(11):B533-6
Telomere shortening with aging in human liver.
  Progressive telomere shortening with aging was studied in the normal
liver tissue of 94 human subjects aged between 0 and 101 years old to
determine the rate of telomere loss in 1 year. Telomere length
demonstrated accelerated shortening with reduction of 55 base pairs (bp)
per year. The mean telomere length in five neonates was 12.9 +/- 2.6
kilobase pairs (kbp), and that in one centenarian was 8.3 kbp. Mean
telomere lengths by age group were 13.2 +/- 2.0 kbp (< or = 8 years; 10
subjects), 7.8 +/- 1.9 kbp (40-79 years; 29 subjects), and 7.5 +/- 2.0
kbp (> or = 80 years; 53 subjects), with reduction thus appearing to show
slowing on the attainment of middle age. The difference of mean telomere
lengths for two groups with or without advanced malignancies of other
than liver origin was not significant in the older two groups. Despite
the slow turnover of liver tissue, the overall reduction rate of telomere
length decrease in 1 year was almost the same as that of digestive tract
mucosa, with its very rapid renewal.

[This helps explain why telomere shortening per cell division varies.]

J Biol Chem. 2000 Jun 30;275(26):19719-22.
Telomere shortening is proportional to the size of the G-rich telomeric
  Most normal diploid human cells do not express telomerase activity and
are unable to maintain telomere length with ongoing cell divisions. We
show that the length of the single-stranded G-rich telomeric 3'-overhang
is proportional to the rate of shortening in four human cell types that
exhibit different rates of telomere shortening in culture. These results
provide direct evidence that the size of the G-rich overhang is not fixed
but subject to regulation. The potential ability to manipulate this rate
has profound implications both for slowing the rate of replicative aging
in normal cells and for accelerating the rate of telomere loss in cancer
cells in combination with anti-telomerase therapies.

[Telomeres make a good biomarker for age, even if the main "cause" of
senescence may lie elsewhere. This article implies that hypoglycemia may
slow aging.]

Neurosci Lett. 2004 Sep 16;368(1):68-72
Exogenous application of glucose induces aging in rat cerebral
oligodendrocytes as revealed by alteration in telomere length.
  To investigate aspects of aging on rat oligodendrocytes, cells of an
oligodendrocyte cell line, so-called OLN-93, were cultured either in the
presence or absence of glucose. Our data demonstrated that
glucose-induced aging in vitro caused an elongation and thickening of
cell processes and significantly increased the expression of netrin
reflecting a more mature state of oligodendrocyte development. A possible
age-inducing effect of glucose is also supported by the decrease of ras
protein expression and shortening of telomeres in glucose-treated
oligodendrocytes. The present study clearly shows that OLN-93 cells are an
exciting and suitable model system for the investigation of age-inducing
molecules and the analysis of signaling pathways involved in cerebral
aging and degenerations.

[Telomere shortening has been used to explain Werner premature aging
symdrone, and even normal human aging. Recently this assumption is
being reviewed.]

Hum Mol Genet. 2004 Jul 15;13(14):1515-24. Epub 2004 May 18.
Normal telomere erosion rates at the single cell level in Werner syndrome
fibroblast cells.
  The aim of this study was to investigate whether the accelerated
replicative senescence seen in Werner syndrome (WS) fibroblasts is due to
accelerated telomere loss per cell division. Using single telomere length
analysis (STELA) we show that the mean rate of telomere shortening in WS
bulk cultures ranges between that of normal fibroblasts [99 bp/population
doubling (PD)] and four times that of normal (355 bp/PD). The telomere
erosion rate in the fastest eroding strain slows in the later stages of
culture to that observed in normal fibroblasts, and appears to be
correlated with a reduction in the heterogeneity of the telomere-length
distributions. Telomere erosion rates in clones of WS cells are much
reduced compared with bulk cultures, as are the variances of the
telomere-length distributions. The overall lack of length heterogeneity
and the normal erosion rates of the clonal populations are consistent with
simple end-replication losses as the major contributor to telomere erosion
in WS cells. We propose that telomere dynamics at the single cell level
in WS fibroblasts are not significantly different from those in normal
fibroblasts, and suggest that the accelerated replicative decline seen in
WS fibroblasts does not result from accelerated telomere erosion.

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