X-Message-Number: 25670
Date: Sun, 6 Feb 2005 20:49:11 -0800 (PST)
From: Doug Skrecky <>
Subject: centenarian fibroblasts surprise gerontologists

[Like the EverReady Energizer bunny, fibroblasts from centenarians just
keep going, and going, and]

Biochem Biophys Res Commun. 1998 Mar 27;244(3):912-6
Growth properties and growth factor responsiveness in skin fibroblasts
from centenarians.
  Human fibroblast cultures, which have a finite replicative lifespan in
vitro, are the most widely used model for the study of senescence at the
cellular level. An inverse relationship between replicative capability
and donor age has been reported in human fibroblast strains. We studied
the growth capacity of fibroblast primary cultures derived from people
whose lifespan was as closer as possible to the expected maximum human
lifespan, i.e. people over one hundred. Our data suggest that outgrowth
of fibroblasts from biopsies, growth kinetics at different population
doubling levels, capability to respond to a classical mitogenic stimulus
(such as 20% serum) and a variety of growth factors, were remarkably
similar in fibroblasts from centenarians and young controls. On the
whole, our data challenge the tenet of a simple and strict relationship
between in vivo aging and in vitro proliferative capability of human
fibroblasts, at least at the individual level.

Biogerontology. 2004;5(6):401-9.
Cloning of differentially expressed genes in skin fibroblasts from
centenarians.
  Normal human fibroblasts undergoing serial passaging have been
extensively used to identify genes linked with aging. Most of the
isolated genes relate to growth retardation signals and the failure of
homeostasis that accompanies aging and senescence. In contrast, there is
still limited knowledge regarding the nature of the genes that influence
positively the rate of aging and longevity. Healthy centenarians
represent the best example of successful aging and longevity. Studies
using samples from these individuals have proved very valuable for
identifying a variety of factors that contribute to successful aging. The
aim of the current work was to take advantage of skin fibroblast cultures
established from healthy donors including centenarians in order to clone
differentially expressed genes in centenarians. First, we demonstrate
that centenarian derived cultures follow the typical Hayflick curve and
they enter senescence after serial passaging. Application of differential
screening techniques in minimally passaged cultures of four control
donors of different ages (18-80 years old) and four centenarians has
resulted in the cloning of six differentially expressed genes in
centenarians. Four of the cloned genes, namely adlican, KBL, EST 38 and
EST 39, were over-expressed in centenarians, while VDUP1 and OCIF were
down-regulated in the same samples. We have also compared the expression
levels of two representative cloned genes in cultures of human embryonic
and adult fibroblasts to establish potential links with replicative
senescence. Interestingly, VDUP1 was found over-expressed in late passage
cells, while EST 39 was down-regulated in the same cultures. Thus our
work demonstrates that a combination of the use of both biopsies derived
cells and classical in vitro cells passaging will facilitate the better
understanding of the biology of aging and longevity.

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