From: Patrick Wilken (patrickw@cs.monash.edu.au)
Date: Thu Aug 26 1999 - 16:35:07 MDT
FOR RELEASE: 26 AUGUST 1999 AT 14:00:00 ET US
University of Wisconsin-Madison
http://www.wisc.edu/
Study details genetic basis of aging -- and how it might be delayed
MADISON, WISC. - Scientists at the University of Wisconsin-Madison have, for
the first time, profiled specific genetic changes during the aging of
experimental animals, a discovery that could aid work to extend life span and
preserve health.
The work conducted with mice combines a powerful new genetic technique with
dietary restriction, the only known way to delay the aging process. The
research will be published Friday, Aug. 27, in the journal Science.
The study is a milestone in aging research, providing scientists with an
intimate look at the ebb and flow of genetic activity with age, and the roles
individual genes play in the process of growing old.
Moreover, it reveals how a low-calorie diet, the only known method of slowing
aging in several animal species, works at the most basic level to extend life
span and preserve health. Such knowledge, used in concert with new technologies
capable of rapidly surveying the activity of thousands of genes at once,
promises to accelerate the development of drugs that mimic the age-retarding
effects of a low-calorie diet, according to the Wisconsin scientists.
The Wisconsin team, led by Tomas A. Prolla, a UW-Madison professor of genetics,
and Richard Weindruch, a UW-Madison professor of medicine, profiled the action
of 6,347 genes. The team charted changes in genetic activity in two groups of
mice, one group on a standard diet and another group whose diet had been
reduced to 76 percent of the standard diet.
"This study has analyzed more genes with regard to aging than all previous
studies combined," Prolla said of the study that surveyed 5 to 10 percent of
the mouse genome using a "gene chip" -- a small glass plate containing DNA
that, when read with a laser, quickly reveals activity levels for thousands of
individual genes.
The Wisconsin group found that, with age, the activity of a very small number
of genes -- less than 2 percent of those surveyed -- changed markedly. But
those genes govern critical biological tasks such as stress responses, protein
repair and energy production, and they changed in big ways.
"At the molecular level, normal aging looks like a state of chronic injury,"
said Prolla.
However, in a big step forward in understanding how a reduced-calorie diet
works to dramatically slow the physical manifestations of aging, many of the
same genes that exhibited changes in activity with aging in mice on a standard
diet remained almost completely intact in mice on a reduced diet.
"This is a leap in our understanding of how caloric restriction works," said
Weindruch, a leading authority in the field of diet and aging. "There hasn't
been much consensus on how caloric restriction retards aging."
Over many years, studies of several animal species have consistently shown that
reduced diets -- 25 to 30 percent less than a typical diet -- retard aging,
extend life span and improve overall health in old age.
The new study, Weindruch said, tends to support the idea that caloric
restriction works by slowing metabolism, the chemical processes by which living
organisms and cells convert food to energy.
In the process of metabolism, some toxic byproducts are produced, damaging
proteins and triggering a stress response that acts to repair damaged molecules
and that seems to be governed by a few select genes. But with age, the body's
ability to repair damaged proteins declines, possibly as a result of shrinking
cellular energy levels.
"Taken as a whole, our results provide evidence that during aging there is an
induction of a stress response as a result of damaged proteins and other
macromolecules," the Wisconsin scientists write in Science. "This response
ensues as the systems required for the turnover of such molecules decline,
perhaps as a result of an energetic deficit in the cell."
The Wisconsin group plans to extend its studies to monkeys and humans.
UW-Madison, at its Wisconsin Regional Primate Research Center, is the site of a
decade-old study of rhesus macaques on a reduced-calorie diet.
The new study, according to Weindruch, is important not only because it
provides a genetic map of aging, but because it shows the potential of
harnessing gene chip technology to screen for the effects of drugs on the
process of growing old.
"It gives us a molecular test to see if an agent can affect the rate of aging,"
said Weindruch. "There are lots of implications. If we can understand the
molecular mechanisms, we could perhaps develop drugs that mimic the effects of
caloric restriction."
Prolla and Weindruch have filed for a patent covering the use of gene chip
technology in aging research through the Wisconsin Alumni Research Foundation.
----------------------------------------------------------------------------
Patrick Wilken
Editor: PSYCHE: An International Journal of Research on Consciousness
Board Member: The Association for the Scientific Study of Consciousness
http://psyche.cs.monash.edu.au/ http://www.phil.vt.edu/ASSC/
This archive was generated by hypermail 2.1.5 : Fri Nov 01 2002 - 15:04:54 MST