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Scientists find path to fountain of youth

2009-10-02 06:37:35

by Jean-Louis Santini Jean-louis Santini Thu Oct 1, 11:10 pm ET

WASHINGTON (AFP) The fountain of youth may exist after all, as a study showed

that scientists have discovered means to extend the lifespan of mice and

primates.

The key to eternal -- or at least prolonged -- youth lies in genetic

manipulation that mimics the health benefits of reducing calorie intake,

suggesting that aging and age-related diseases can be treated.

Scientists from the Institute of Healthy Ageing at University College London

(UCL) extended the lifespan of mice by up to a fifth and reduced the number of

age-related diseases affecting the animals after they genetically manipulated

them to block production of the S6 Kinase 1 (S6K1) protein.

Scientists have shown since the 1930s that reducing the calorie intake by 30

percent for rats, mice and -- in a more recent finding -- primates can extend

their lifespan by 40 percent and have health benefits.

By blocking S6K1, which is involved in the body's response to changes in food

intake, similar benefits were obtained without reducing food intake, according

to the study published in the US journal Science.

The results corroborated those of other recent studies.

"Blocking the action of the S6K1 protein helps prevent a number of age-related

conditions in female mice," explained UCL professor Dominic Withers, the

study's lead author.

"The mice lived longer and were leaner, more active and generally healthier

than the control group. We added 'life to their years' as well as 'years to

their lives.'"

The genetically altered female mice lived 20 percent longer -- living a total

of 950 days -- or over 160 days more than their normal counterparts.

At age 600 days, the equivalent of middle age in humans, the altered female

mice were leaner, had stronger bones, were protected from type 2 diabetes,

performed better at motor tasks and demonstrated better senses and cognition,

according to the study.

Their T-cells, a key component of the immune system also seemed more

"youthful," the researchers said, which points to a slowing of the declining

immunity that usually accompanies aging.

Male mice showed little difference in lifespan although they also demonstrated

some of the health benefits, including less resistance to insulin and healthier

T-cells. Researchers said reasons for the differences between the two sexes

were unclear.

"We are suddenly much closer to treatments for aging than we thought," said

David Gems of UCL's Institute of Healthy Aging, one of the authors of the

study, which was primarily funded by the Wellcome Trust.

"We have moved from initial findings in worm models to having 'druggable'

targets in mice. The next logical step is to see if drugs like metformin can

slow the aging process in humans."

Other studies have also found that blocking S6K1 were channeled through

increased activity of a second molecule, AMPK, which regulates energy levels

within cells.

AMPK, also known as a master "fuel gauge," is activated when cellular energy

levels fall, as takes place when calorie intake is reduced.

Drugs, such as the widely-used metformin, that activate AMPK are already being

used in human patients to treat type 2 diabetes.

Recent studies by Russian scientists suggested that metformin can extend mice's

lifespan.

Another drug, rapamycin, was found to extend the lifespan of mice, according to

a study published in the British journal Nature.

As rapamycin is already used in humans as an immunosuppresant -- to prevent a

patient from rejecting an organ after transplant -- it could not be

administered as an anti-ageing drug in its current form.

But rapamycin blocks S6K1 activity and could thus extend lifespan through its

impact on S6K1.

Seizing on the potential, US firm Sirtris Pharmaceuticals uses resveratrol, a

powerful anti-oxidant found in red wine, as well as other fruits than raisin.

Sirtris scientists -- including co-founder David Sinclair, also a researcher at

Harvard Medical School -- have found that resveratrol activates the production

of sirtuin proteins, which also unleash the same physiological effects as

reducing calorie intake.

Sirtris has produced highly concentrated doses of resveratrol and is currently

leading clinical trials with diabetes patients and others suffering from liver

and colon cancer.