X-Message-Number: 24821
Date: Fri, 15 Oct 2004 19:29:02 -0700 (PDT)
From: Doug Skrecky <>
Subject: telomere dependant human aging

Hypertens Res. 2004 May;27(5):319-25.
Telomere attrition in white blood cell correlating with cardiovascular damage.
  Aging is a major risk factor for cardiovascular disease. Chronological
aging does not always parallel biological aging, but there is no reliable
biomarker for the latter. In the present study, we tested the hypothesis
that telomere attrition in white blood cells is related to endothelial
dysfunction and the extent of atherosclerosis, and thus may serve as a
useful marker for biological aging. We evaluated telomere lengths in
white blood cells by measuring the mean telomere restriction fragment
length (mTRFL), as well as endothelial function by flow mediated
dilatation (FMD) in the brachial artery, in patients with various degrees
of cardiovascular damage and in normal subjects. Cardiovascular damage
was assessed by a cardiovascular damage (CVD) score, with 1 point being
given for the presence of each cardiovascular risk factor (hypertension,
hyperlipidemia and diabetes) and for each event (angina, myocardial
infarction, cerebrovascular event and peripheral vascular disease).
Subset analysis of CVD score groups revealed that mTRFL and FMD decreased
in the rank order of CVD score. Although mTRFL was inversely correlated
with age, telomere index, defined as the ratio of TRFL to
TRFL predicted by age, also decreased with increase in CVD score. These
results indicate that telomere attrition in white blood cells is more
closely associated with endothelial damage and atherosclerosis than is
chronological aging, supporting the hypothesis that mTRFL in white blood
cells is a useful marker for biological aging of the cardiovascular

EMBO J. 2003 Jan 2;22(1):131-9.
Ablation of telomerase and telomere loss leads to cardiac dilatation and
heart failure associated with p53 upregulation.
  Cardiac failure is a frequent cause of death in the aging human
population. Telomere attrition occurs with age, and is proposed to be
causal for the aging process. To determine whether telomere shortening
leads to a cardiac phenotype, we studied heart function in the telomerase
knockout mouse, Terc-/-. We studied Terc-/- mice at the second, G2, and
fifth, G5, generation. Telomere shortening in G2 and G5 Terc-/- mice was
coupled with attenuation in cardiac myocyte proliferation, increased
apoptosis and cardiac myocyte hypertrophy. On a single-cell basis,
telomere shortening was coincidental with increased expression of p53,
indicating the presence of dysfunctional telomeres in cardiac myocytes
from G5 Terc-/- mice. The impairment in cell division, the enhanced
cardiac myocyte death and cellular hypertrophy, are concomitant with
ventricular dilation, thinning of the wall and cardiac dysfunction. Thus,
inhibition of cardiac myocyte replication provoked by telomere
shortening, results in de-compensated eccentric hypertrophy and heart
failure in mice. Telomere shortening with age could also contribute to
cardiac failure in humans, opening the possibility for new therapies.

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