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Tests raise life extension hopes
07-10-2009, 02:19 AM,
#1
Tests raise life extension hopes
Tests raise life extension hopes

A drug discovered in the soil of a South Pacific island may help to fight the ageing process, research suggests.

When US scientists treated old mice with rapamycin it extended their expected lifespan by up to 38%.

[Image: _46026185_easter.jpg]
Rapamycin was discovered on Easter Island

The findings, published in the journal Nature, raise the prospect of being able to slow down the ageing process in older people.

However, a UK expert warned against using the drug to try to extend lifespan, as it can suppress immunity.

“ We believe this is the first convincing evidence that the ageing process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age. ”
Professor Randy Strong University of Texas

Rapamycin was first discovered on Easter Island in the 1970s.

It is already used to prevent organ rejection in transplant patients, and in stents implanted into patients to keep their coronary arteries open. It is also being tested as a possible treatment for cancer.

Researchers at three centres in Texas, Michigan and Maine gave the drug to mice at an age equivalent to 60 in humans.

The mice were bred to mimic the genetic diversity and susceptibility to disease of humans as closely as possible.

Rapamycin extended the animals' expected lifespan by between 28% and 38%.

The researchers estimated that in human terms this would be greater than the predicted increase in extra years of life, if both cancer and heart disease were prevented and cured.

Researcher Dr Arlan Richardson, of the Barshop Institute, said: "I've been in ageing research for 35 years and there have been many so-called 'anti-ageing' interventions over those years that were never successful.

"I never thought we would find an anti-ageing pill for people in my lifetime; however, rapamycin shows a great deal of promise to do just that."

Professor Randy Strong, of the University of Texas Health Science Center, said: "We believe this is the first convincing evidence that the ageing process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age."

Calorie restriction

Rapamycin appears to have a similar effect to restricting food intake, which has also been shown to boost longevity.

“ In no way should anyone consider using this particular drug to try to extend their own lifespan, as rapamycin suppresses immunity ”
Dr Lynne Cox University of Oxford

It targets a protein in cells called mTOR, which controls many processes involved in metabolism and response to stress.

The researchers had to find a way to re-formulate the drug so that it was stable enough to make it to the mice's intestines before beginning to break down.

The original aim was to begin feeding the mice at four months of age, but the delay caused by developing the new formulation meant that feeding did not start until the animals were 20 months old.

The researchers thought the animals would be too old for the drug to have any effect - and were surprised when it did.

Professor Strong said: "This study has clearly identified a potential therapeutic target for the development of drugs aimed at preventing age-related diseases and extending healthy lifespan.

"If rapamycin, or drugs like rapamycin, works as envisioned, the potential reduction in health cost will be enormous."

'Don't try it now'

Dr Lynne Cox, an expert in ageing at the University of Oxford, described the study as "exciting".

She said: "It is especially interesting that the drug was effective even when given to older mice, as it would be much better to treat ageing in older people rather than using drugs long-term through life."

However, she added: "In no way should anyone consider using this particular drug to try to extend their own lifespan, as rapamycin suppresses immunity.

"While the lab mice were protected from infection, that's simply impossible in the human population.

"What the study does is to highlight an important molecular pathway that new, more specific drugs might be designed to work on.

"Whether it's a sensible thing to try to increase lifespan this way is another matter; perhaps increasing health span rather than overall lifespan might be a better goal."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/8139816.stm
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07-10-2009, 02:38 AM,
#2
Tests raise life extension hopes
Published online 8 July 2009 | Nature | doi:10.1038/news.2009.648

News
A pill for longer life?

A drug slows the march of time in middle-aged mice.

Kerri Smith
Elderly peopleCould a pill one day slow ageing in humans?Punchstock

Rapamycin, a drug commonly used in humans to prevent transplanted organs from being rejected, has been found to extend the lives of mice by up to 14% — even when given to the mice late in life.

In flies and worms, drug treatments have been shown to prolong lifespan, but until now, the only robust way to extend life in mammals has been to heavily restrict diet.

The researchers caution, however, that using this drug to extend the lifespan of humans might be problematic because it suppresses the immune system — potentially making people who take it more susceptible to infectious diseases.

Research teams at three different US institutions — the University of Texas Health Science Center in San Antonio, the University of Michigan in Ann Arbor and the Jackson Laboratory in Bar Harbor, Maine — ran the same experiment in parallel, splitting nearly 2,000 mice between them. The mice were bred to ensure that they were genetically different enough that no single strain would be more or less susceptible to ageing-related diseases or the effects of the drug. They then gave the mice food that included rapamycin.

Problems formulating the feed meant that the teams couldn't start the treatment until the mice were rather older than they had planned — 20 months of age, or the equivalent of about 60 years in human terms.

As it happened, this delay was a fortuitous accident. Compared with the non-drug-taking group, the lifespans of the mice given rapamycin increased by up to 14%, even though they were middle-aged when treatment began. Their life expectancy at 20 months shot up by 28% for the males and 38% for the females.1

"You've probably heard the phrase 'chance favours the prepared mind', and this is an example of it," says David Harrison, who led the arm of the experiment that took place at the Jackson Laboratory.
Calorie control link?

An independent initiative, the Interventions Testing Program overseen by the US National Institute of Aging, chose rapamycin for the three labs to test because it's known to have effects on a cellular pathway called TOR (for target of rapamycin). This pathway is known from studies in mice, flies and worms to be involved in the age-defying effects of calorie-restricted diets.

“I wouldn't do it myself and wouldn't encourage anyone to do it at this point.”

David Harrison
Jackson Laboratory

This link could mean that rapamycin is mimicking the effects of dietary restriction, says Matt Kaeberlein, whose group at the University of Washington in Seattle works on ageing in mice, yeast and worms. "All the arrows are going in the right direction," he says.

Harrison isn't so sure, however — none of the mice lost body weight during their experiments, he says, and dietary restriction usually works best when started early in life, not in middle age as the rapamycin treatment was.

The big question, of course, is whether this drug could extend human life. Both Harrison and Kaeberlein are cautious. "I wouldn't do it myself and wouldn't encourage anyone to do it at this point," says Harrison.

Getting the dose correct is another problem. A normal human dose of rapamycin is between 2 and 5 milligrams per day, much lower than the dose given to the mice, which was 2.24 milligrams per kilogram of body weight per day.

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Perhaps rapamycin could be altered somehow, to reduce its effects in the immune system while keeping its anti-ageing effects? "It's an open question whether you can uncouple that from immune suppression," Kaeberlein says. But in future, he says, it's likely that it will be possible to tweak rapamycin in this way, or to target the other molecules in the pathway instead. Kaeberlein's lab is already working on these downstream targets.

Several other compounds are currently being tested by the three US centres as part of the Interventions Testing Program, including resveratrol, a compound found in red wine and thought to have beneficial effects on the heart, and simvastatin, one of a family of compounds called statins, also used for heart conditions.

For now, the researchers won't be trying out their anti-ageing drug on themselves. But that hasn't stopped them daydreaming about it. "Of course, you can imagine we've been considering it ourselves," laughs Harrison. "I'm 67, so it's just about time for me to start my treatment, isn't it?"

http://www.nature.com/news/2009/090708/ful...s.2009.648.html
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