/-------------------- advertisement -----------------------\
Explore more of Starbucks at Starbucks.com.
http://www.starbucks.com/default.asp?ci=1015
\----------------------------------------------------------/
Study Spurs Hope of Finding Way to Increase Human Life
August 25, 2003
By NICHOLAS WADE
Biologists have found a class of chemicals that they hope
will make people live longer by activating an ancient
survival reflex. One chemical, a natural substance known as
resveratrol, is found in red wines, particularly those made
in cooler climates like that of New York State.
The finding could help explain the so-called French paradox
- the fact that the French consume fatty foods considered
threatening to the heart but live as long as anyone else.
Besides the wine connection, the finding has the attraction
of stemming from fundamental research in the biology of
aging. However, the new chemicals have not yet been tested
even in mice, let alone people, and even if they work in
humans it will be many years before any drug based on the
new findings becomes available.
The possible benefits could be significant. The chemicals
are designed to mimic the effect of a very low-calorie
diet, which is known to lengthen the life span of rodents.
Scientists involved in the research say human life span
could be extended by 30 percent if people respond to the
chemicals the way rats and mice do to low calories. Even
someone who started at age 50 to take one of the new
chemicals could expect to gain an extra 10 years of life,
said Dr. Leonard Guarente of the Massachusetts Institute of
Technology, one of the pioneers of the new research.
The result was announced last week at a scientific
conference in Arolla, a small village in the Swiss Alps, by
Dr. David A. Sinclair of Harvard Medical School. It was
published electronically yesterday in the journal Nature.
The new development has roused the enthusiasm of many
biologists who study aging because caloric restriction, the
process supposedly mimicked by the chemicals, is the one
intervention known to increase longevity in laboratory
animals. A calorically restricted diet - including all
necessary nutrients but 30 percent fewer calories than
usual - has been found to extend the life span of rodents
by 30 to 50 percent. Scientists hope, but do not yet know,
that the same will be true in people.
A similar mechanism exists in simpler forms of life, which
has led biologists to believe that they are looking at an
ancient strategy, formed early in evolution and built into
all animals. The strategy allows an organism to live longer
and postpone reproduction when food is scarce, and to start
breeding when conditions improve.
Two experiments to see if caloric restriction extends life
span in monkeys are at about their halfway point - rhesus
monkeys live some 25 years in captivity - and the signs so
far are promising, though not yet statistically
significant. But even if caloric restriction should extend
people's life span, the current epidemic of obesity
suggests how hard it would be for most people to stick with
a diet containing 30 percent fewer calories than generally
recommended.
Biologists have therefore been hoping to find some chemical
or drug that would mimic caloric restriction in people by
tripping the same genetic circuitry that a reduced-calorie
diet does and provide the gain without the pain. Dr.
Sinclair and his chief co-author, Dr. Konrad T. Howitz of
Biomol Research Laboratories in Plymouth Meeting, Pa., say
they have succeeded in finding a class of drugs that mimic
caloric restriction in two standard laboratory organisms,
yeast and fruit flies. Mice and humans have counterpart
genes that are assumed to work in a similar way, though
this remains to be proved.
Independently, Elixir Pharmaceuticals of Cambridge, Mass.,
had found a different set of chemicals that mimic caloric
restriction, said Ed Cannon, Elixir's chief executive.
Because of testing and regulatory requirements, he added,
his company is "8 to 10 years away from having an approved
drug."
After presenting his results for the first time, Dr.
Sinclair said in an interview from Arolla, "I've been
waiting for this all my life."
"I like to be cautious," he added, "but even as a scientist
it is looking extremely promising."
So far Dr. Sinclair and his colleagues have shown only that
resveratrol, the chemical found in red wine, prolongs life
span in yeast, a fungus, by 70 percent. But a colleague,
Dr. Mark Tatar of Brown University, has shown, in a report
yet to be published, that the compound has similar effects
in fruit flies. The National Institute of Aging, which
sponsored Dr. Sinclair's research, plans to start a mouse
study later in the year.
Despite the years of testing that will be needed to prove
that resveratrol has any effect in people, many of the
scientists involved in the research have already started
drinking red wine. "One glass of red wine a day is a good
recommendation. That's what I do now," Dr. Sinclair said.
Resveratrol, he said, is unstable on exposure to the air
and "goes off within a day of popping the cork."
Dr. Tatar, asked if he had changed his drinking habits,
said, "No, I have always preferred red wine to white."
Health authorities have not had time to make a detailed
evaluation of the research. Dr. David Finkelstein, the
project officer at the National Institute of Aging, said he
would not advise anyone to start drinking red wine.
"At this point we have no indication that there will be a
benefit in people," Dr. Finkelstein said, adding that the
calories in a glass of wine could lead to weight gain.
Dr. Toren Finkel, who is in charge of cardiovascular
research at the National Heart, Lung and Blood Institute,
said: "I would be cautious in sending out the message that
one glass of wine a day will make you live 10 years longer.
The concentration of resveratrol in different wine differs.
As a drug, it is not ready for prime time." But the concept
of a drug that mimics caloric restriction "is a great
idea," he said.
Dr. Sinclair said that he and Dr. Howitz were working on
chemical modifications of resveratrol that would be more
stable. Ownership of the patent will be split evenly
between their parent institutions, Harvard Medical School
and Biomol.
Resveratrol is synthesized by plants in response to stress
like lack of nutrients and fungal infection. It exists in
the skin of both red and white grapes but is found in
amounts 10 times as high in red wine as in white because of
the different manufacturing process.
According to "The Oxford Companion to Wine," pinot noir
tends to have high levels of the chemical, cabernet
sauvignon lower levels. "Wines produced in cooler regions
or areas with greater disease pressure such as Burgundy and
New York often have more resveratrol," the book says,
whereas wines from drier climates like California or
Australia have less.
Besides resveratrol, another class of chemical found to
mimic caloric restriction is that of the flavones, found
abundantly in olive oil, Dr. Howitz said.
The enthusiasm scientists are showing for the discovery,
despite its preliminary nature, stems in part from a train
of discoveries stretching back a decade. In 1991 Dr.
Guarente decided to study the basis of aging, then
considered an intractable and unpromising field of
research. He spent four years searching for strains of
yeast, a common laboratory organism, that lived longer than
others. By 1997, he and Dr. Sinclair, who worked in his
laboratory at the time, had discovered the reason for the
new strains' longevity. It centered on a gene called sir2,
for silent information regulator No. 2.
Dr. Guarente next found that when yeast cells live longer
because of starvation, sir2 is the gene that mediates the
response. His research then started to fuse with
longstanding work on caloric restriction as he and others
showed that starvation is sensed by sir2, which sets off
the cellular changes that lead to increased life span.
Dr. Sinclair and Dr. Howitz took the human version of
sirtuin, the enzyme produced by the sir2 gene, and devised
a test to tell when the enzyme was activated. They then
screened a large batch of likely chemicals to see if any
made the enzyme more active.
Their screening produced two active chemicals, both
belonging to the family known as polyphenols. That led them
to expand the search to more polyphenols. The most active
compound in the second screen was resveratrol.
Dr. Sinclair said he was amazed "that in an unbiased screen
we pulled out something already associated with health
benefits."
Much attention has been paid to resveratrol in the last few
years, because it is a candidate for explaining the
apparent innocuousness of the French diet despite its
artery-weakening ingredients. Epidemiological studies point
to red wine as containing some beneficial antidote, but it
is not yet certain whether alcohol, resveratrol or a
combination of the two is the active ingredient.
Dr. Guarente, Dr. Sinclair's former mentor, founded Elixir
Pharmaceuticals to pursue the same goal of developing drugs
that mimic caloric restriction. He said diet-mimicking
drugs might add a decade of life to someone starting them
at age 50, based on the calculation that the 30 or so
additional years of life expected at that age could be
increased by one-third, and assuming that humans would
benefit from caloric restrictions to the same degree as
mice.
Elixir uses the same screen for sirtuin activity as Dr.
Sinclair did, one provided by Biomol. It is not yet clear
if the efforts of Dr. Sinclair and Elixir will be
competitive or collaborative, Dr. Howitz said.
In either case, considerable testing lies ahead to see if
the promise of the new research can be fulfilled.
http://www.nytimes.com/2003/08/25/science/25LIFE.html?ex=1062839144&ei=1&en=18a360371898bc1c
---------------------------------
Get Home Delivery of The New York Times Newspaper. Imagine
reading The New York Times any time & anywhere you like!
Leisurely catch up on events & expand your horizons. Enjoy
now for 50% off Home Delivery! Click here:
http://www.nytimes.com/ads/nytcirc/index.html
HOW TO ADVERTISE
---------------------------------
For information on advertising in e-mail newsletters
or other creative advertising opportunities with The
New York Times on the Web, please contact
[EMAIL PROTECTED] or visit our online media
kit at http://www.nytimes.com/adinfo
For general information about NYTimes.com, write to
[EMAIL PROTECTED]
Copyright 2003 The New York Times Company
Enter for your chance to IM with Bon Jovi, Seal, Bow Wow, or Mary J Blige using MSN Messenger -------------------------------------------- This service is hosted on the Infocom network http://www.infocom.co.ug
