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Great article on the status of the Wisconsin rhesus monkey
study in the
MIT Technology Review:

http://www.technologyreview.com/read_article.aspx?id=17572&ch=biotech

Titled: Do Dieting Monkeys Live Healthier and Longer Lives?

Preliminary evidence from one of the largest studies of
calorie-restricted diet in primates shows health benefits.

"An ongoing study at the University of Wisconsin-Madison in
which rhesus monkeys are being fed an extremely
calorie-restricted diet gives preliminary evidence that the
regime prevents age-related diseases. For decades,
scientists have known that a diet of about 30-percent fewer
calories than normal extends the lifespan of mice by 10 to
20 percent, reduces their incidence of cancer, and prevents
the deterioration of learning and memory in the rodents. And
similar effects have been shown in lower organisms from
yeast to fruit flies. But such life extension has not been
proven yet in primates.


Researchers at the Wisconsin National Primate Research
Center have been studying a group of 76 rhesus monkeys, half
of them on calorie restriction and half on a normal diet,
for 18 years, to determine whether or not the restricted
diet has the same health benefits in primates as it does in
other animals. The study will likely go on for at least
another decade, since the monkeys are only now entering old
age. Captive rhesus monkeys usually live to around 25 years
old, which is now about the average age of the monkeys in
the study. An age of 40 for a rhesus monkey is similar to
120 for a human--the apparent maximum lifespan.


Although there is now strong evidence that caloric
restriction prevents diabetes in the primates (the disease
is a major killer of captive rhesus monkeys), it's still too
early to assess the diet's effects on their lifespan,
according to Richard Weindruch, professor of medicine at the
University of Wisconsin, who is heading up the study.


But preliminary evidence suggests that the diet is
preventing loss of muscle mass, arthritis, menstrual
irregularities, and other signs of aging. "Over the next 10
years, survival differences will come out," predicts Ricki
Colman, a scientist on the study. Meanwhile, eight of the
monkeys on a normal diet have died of age-related causes
such as cancer and diabetes; five on the restricted diet
have died of these causes.


As the monkeys enter old age, the researchers are beginning
gene expression profiling on them--the first step toward
finding the molecular mechanisms that connect the extreme
diet to its effects in the animals. The monkeys will also
undergo MRIs and be tested for mental acuity, to assess
whether or not the diet prevents age-related deterioration
of learning and memory.


Even if a diet of 30-percent fewer calories proved to extend
healthy human lifespan, however, it's unlikely that most
people could be able to stick with it. (A group of
individuals following such a diet, called the Calorie
Restriction Society, seem to have some health benefits. See
"Human Study Shows Benefits of Caloric Restriction".)


Researchers studying caloric restriction in animals,
including Colman, say that, in general, such a diet is "not
a long-term possibility in humans." Rather, the primary goal
of their study, Colman and Weindruch agree, is to learn
about aging and to understand how caloric restriction
changes metabolism and gene expression.



To make sure the study is as applicable to humans as
possible, the Wisconsin scientists provide the monkeys with
human-like health care: diabetic monkeys are given insulin;
the animals get dental care; and female monkeys suffering
endometriosis--a painful condition of the uterine lining
common to humans--may undergo surgery. The only other study
of caloric restriction in nonhuman primates, at the National
Institute on Aging, is larger (120 monkeys) and two years
longer-running than the Wisconsin study. However, it may not
be as applicable to humans because those monkeys are not
given extensive medical care, and were put on their
restricted diets at a much younger age, some immediately
after weaning, which stunts growth, according to Colman.


The Wisconsin researchers use all human medical equipment on
the monkeys, Colman says, including an MRI scanner for
upcoming brain-imaging studies. Each monkey will have two
scans over a five-year period to monitor changes. Because
caloric restriction's effects on the body seem to be
general, there's no reason it shouldn't be good for the
brain if it's good for other organs, says Sterling Johnson,
assistant professor of medicine at the University of
Wisconsin. Normal aging is accompanied by a slight decrease
in brain volume, he says.


When the monkeys die, samples of their brain tissue will be
saved for future studies of caloric restriction's effects on
gene expression in that organ, Johnson says. As mice age,
genes associated with inflammation and the death of brain
cells, for example, become more active, while many of those
associated with metabolism become less active. Studies of
aging in calorie-restricted mice in Weindruch's lab have
demonstrated that the diet prevents about 70 percent of such
age-related changes.


In 2001, when the rhesus monkeys were middle-aged, Weindruch
published a study showing that, although differences in gene
expression existed between those primates on caloric
restriction and the control group, the diet did not seem to
prevent age-related changes in gene expression. Weindruch
expects to get different results when his group does another
round of tests, however, now that the monkeys are truly
old--and now that technology exists to test specifically for
rhesus monkey genes. In the previous round of testing,
Weindruch and colleagues had to use chips with human genes
on them, since rhesus monkey chips became available only
recently.


Whatever the mechanisms turn out to be, "there's something
that happens with that extra reduction of food intake that
really affects the aging process," says Joseph Kemnitz,
director of the Wisconsin primate research center.
Ultimately, the researchers hope to take what they learn
about this process to help people maintain a high quality of
life throughout old age."