Caloric restriction slows brain aging

Lou Pagnucco pagnucco at oeonline.com
Tue Jun 27 22:36:11 EST 2000

Below is a summary of a paper just published in
Nature Genetics which demonstrates that genes
(at least in lab mice) that are upregulated during
aging in the brain (associated with inflammation and
the stress response) are repressed by caloric
restriction.  Presumably, CR should retard brain

It is interesting that gene chips were central to this
analysis.   The secrets of the aging process are finally
being unraveled.

L. Pagnucco

>From URL:

Eating Less Seems To Fend Off Brain Diseases

Eating less may be good for the health of your brain, and
may help keep debilitating ailments such as Alzheimer's
and Parkinson's diseases at bay.

That is the message derived from a pathbreaking study
that employed a powerful new gene-scanning technique
to analyze activity in thousands of genes to create a
molecular portrait of the aging brain in mice.

The new study focuses on genetic activity related to two
critical regions of the brain: the cerebral cortex, the part
of the brain involved in the higher functions of thought, and
the cerebellum, the brain structure that helps coordinate
motor and muscle function.

Conducted by scientists at the University of Wisconsin-
Madison and to be reported in July in the British scientific
journal Nature Genetics, the study provides new insight into
the cognitive and motor skill deficits that occur with age.

The results may also help to explain the basis of common
neurological disorders such as Parkinson's and Alzheimer's

Cheol-Koo Lee, Richard Weindruch and Tomas A. Prolla,
all of UW-Madison, profiled the action of 6,347 genes. The
scientists charted changes in genetic activity in two groups of
aging mice, one group on a standard diet and another group
whose diet had been trimmed to 76 percent of the standard diet.

The study builds on similar work of aging skeletal muscle by the
same group of Wisconsin scientists and reported last year in the
journal Science.

The new Wisconsin study shows that a reduced-calorie diet
selectively lowers the age-associated increase in the activity of
genes that encode inflammatory and free-radical-generated
stress responses, says Weindruch, a UW-Madison professor
of medicine.

Free radicals are highly reactive molecules that circulate in the
body and can damage cells over time. Previous studies suggest
that both inflammation and free-radical damage may play a role
in the onset of Alzheimer's and Parkinson's disease.

The study's findings, Weindruch notes, add to mounting evidence
that a reduced-calorie diet, the only known method of slowing
aging in several species of animals, not only extends life, but
confers health benefits that contribute significantly to a better
quality of life in old age.

The study also suggests that basic aging mechanisms in the
brain, including inflammation and free radical damage, are
shared among different species of animals, including mice,
monkeys and humans.

Scientific opinion on the value of the mouse as a model for
human neurological disorders is divided, says Prolla, a
UW-Madison professor of genetics. But the Wisconsin study
shows that many genes related to inflammation become more
active with normal aging, a phenomenon suppressed in mice
placed on a low-calorie diet.

"Although it is known that caloric restriction retards certain
aspects of aging in the brain, the mechanism is not known,"
says Weindruch, an authority on caloric restriction and aging.
"However, these new findings advance our understanding of
caloric restriction's effects on aging in the brain."

Prolla says this new understanding of the relationship between
genes and brain health in mice could take on importance as a
testing ground for new drugs: "It means we can use mice to
screen for drugs that might prevent these processes in humans,"
Prolla says.

"Gene expression changes observed with aging in the two
brain regions can be used to measure the aging process on
a tissue-specific and molecular basis," Weindruch says.
"This should facilitate the development of interventions --
drugs, dietary modifications -- to retard aging in the brain."

Prolla says the study also indicates that diet alterations may
lower the risk of developing some of the most common and
debilitating age-associated neurological disorders.

The Wisconsin study depended on a powerful new technology
known as the "gene chip," a small DNA-laden plate that, when
read with a laser, reveals activity levels for thousands of
individual genes at once. The technique can show which genes
are in play in a given circumstance. The more than 6,000
genes surveyed for the new Wisconsin study represent
5 percent to 20 percent of the mouse genome.

The Wisconsin group is extending its gene chip 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.
- By Terry Devitt

[Contact: Richard Weindruch, Tomas A. Prolla, Terry Devitt ]

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