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Fraggle145
7/8/2009, 02:13 PM
This is cutting edge stuff here... This is the news article about a paper that just came out in the science journal nature:


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

Kerri Smith

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.

"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.

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.

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?"

Fraggle145
7/8/2009, 02:19 PM
This is another article about it that is in the journal itself:


Ageing: A midlife longevity drug?

Matt Kaeberlein1 & Brian K. Kennedy1

1. Matt Kaeberlein and Brian K. Kennedy are in the Departments of Pathology and Biochemistry, University of Washington, Seattle, Washington 98195, USA. Email: [email protected]

Abstract

The small molecule rapamycin, already approved for clinical use for various human disorders, has been found to significantly increase lifespan in mice. Is this a step towards an anti-ageing drug for people?

Anti-ageing drugs — compounds that slow the hands of time and allow humans to live far beyond their natural span — have long been fertile ground for science-fiction writers. More recently, however, the possibility that such compounds might exist, and might perhaps even be within reach, has gained scientific credibility. In a Nature paper published online today, Harrison et al.1 provide evidence that pharmacological intervention in the ageing process is feasible in mammals. They report that dietary supplementation with rapamycin — a compound known to be linked to lifespan in invertebrates — significantly increases the lifespan of mice.

The US National Institute on Aging's Interventions Testing Program (ITP) was designed to test compounds of interest for effects on ageing in mice1. Anyone from the scientific community can nominate a compound for consideration by the ITP, and selected compounds are tested in parallel longevity studies at laboratories at three sites, providing built-in triplicate replication and high statistical power. Several compounds have already been tested. Of these, rapamycin is the first to robustly increase lifespan across all three centres and in both male and female mice.

As is often the case in science, this study benefited from a fortuitous accident. Early on, the ITP researchers realized that simply adding rapamycin to feed failed to maintain high levels of the drug, so a specially formulated feed was developed in which rapamycin is encapsulated for timed release in the intestine. It took more than a year to develop the special feed, which meant that mice in the first cohort to receive rapamycin were 600 days old when supplementation was initiated. As Harrison et al.1 note, this is "roughly the equivalent of a 60-year-old person". Amazingly, both the median and maximum lifespan of these middle-aged mice were significantly increased by rapamycin supplementation. For instance, rapamycin increased maximum lifespan (defined by the 90th survival percentile) from 1,094 days to 1,245 days for female mice and from 1,078 days to 1,179 days for male mice. This translates into a striking increase in life expectancy at the time rapamycin supplementation was initiated of about 38% for females and 28% for males. In an ongoing study, mice are being fed rapamycin beginning at 270 days, with a significant increase in survival also being apparent in this cohort.

Rapamycin was first identified as a natural product of the bacterium Streptomyces hygroscopicus in soil samples from Easter Island — famous for its impressive rock-carved human statues (Fig. 1).
http://www.nature.com.ezproxy.lib.ou.edu/nature/journal/vaop/ncurrent/images/nature08246-f1.2.jpg
Rapamycin, the compound shown by Harrison et al.1 to prolong lifespan in mice, was first identified in soil samples taken on Easter Island, the Polynesian island famed for its rock-carved figures. Rapamycin compounds are used clinically as immunosuppressants for organ transplants, as a treatment for advanced kidney cancer, and to prevent narrowing of coronary arteries after angioplasty. Easter Island is also known as Rapa Nui, from where rapamycin gets its nameThe compound was selected for inclusion in the ITP on the basis of its known property as an inhibitor of the kinase enzyme, target of rapamycin (TOR). TOR signalling has previously been linked to the ageing process in invertebrates2, 3, 4, 5, 6, but until now it had remained an open question as to whether TOR signalling also has a central role in mammalian ageing. The findings of Harrison et al.1 make TOR the first protein that has been shown to modulate lifespan in each of the four model organisms most commonly used to study ageing: yeast, worms, flies and mice7.

How does TOR activity influence ageing? Among other functions, TOR promotes translation of messenger RNA into protein by the ribosome, and inhibits a pathway that degrades cellular products in lysosomal vesicles (autophagy) — both of which have been implicated in ageing in invertebrate species7. Regulation of mRNA translation by TOR, in particular, has emerged as a lifespan-determining pathway that is highly conserved between yeast and the nematode worm Caenorhabditis elegans. In both species, mutations in targets of TOR, such as ribosomal S6 kinase (an enzyme involved in protein translation), several translation-initiation factors and multiple ribosomal proteins, increase lifespan8. In addition, TOR influences cell growth, cell-cycle progression, mitochondrial metabolism and insulin-like signalling. Untangling the relative contributions of each of these processes to the lifespan extension in mice conferred by rapamycin is likely to stimulate much interest during the next few years.

TOR signalling has also received attention for its role as a possible mediator of dietary restriction. This is defined as a reduction in nutrient availability without malnutrition, and has long been known to increase lifespan in species ranging from yeast to rodents7. TOR activity is reduced by dietary restriction, and genetic studies in invertebrate models have linked the inhibition of TOR to increased longevity by dietary restriction7. For example, a recent study in yeast showed that TOR inhibition increases the amounts of a nutritionally responsive transcriptional activator Gcn4, and demonstrated that this is required for full lifespan extension from dietary restriction9. Similarly, autophagy must be induced for lifespan to be extended by dietary restriction in C. elegans10.

On the basis of these studies, it is tempting to speculate that rapamycin may be functioning as a dietary-restriction mimetic — a small molecule that provides the benefits of dietary restriction without requiring a reduction in food intake. Like dietary restriction, TOR inhibition not only increases lifespan, but also confers protection in invertebrate and rodent models against age-associated disorders, including cardiovascular dysfunction, diet-induced obesity and cancer7. Cancer inhibition in particular is a hallmark of dietary restriction in rodents, and rapamycin analogues are already used clinically as a treatment for certain forms of cancer.

Despite these links, Harrison et al.1 do not strongly favour the idea that rapamycin is mimicking dietary restriction in mice. This is based on their data that rapamycin extends lifespan without reducing body weight, and when treatment is initiated during middle age (late-life onset of dietary restriction has shown inconsistent effects on longevity in previous studies). It is worth pointing out, however, that a true dietary-restriction mimetic may not reduce body weight if it mimics the signalling events (and downstream responses) associated with dietary restriction without changing food consumption. Also, dietary restriction has not yet been extensively characterized in mice of the genetically diverse background used by Harrison et al., so it is difficult to predict whether dietary restriction in these animals would have effects similar to rapamycin. Thus, although it is premature to say for certain that rapamycin is functioning as a dietary-restriction mimetic in mice, the known role of TOR in the nutrient response, and the genetic relationship between TOR signalling and dietary restriction in invertebrates, make this a reasonable possibility.

Is this the first step towards an anti-ageing drug for people? Certainly, healthy individuals should not consider taking rapamycin to slow ageing — the potential immunosuppressive effects of this compound alone are sufficient to caution against this. On the basis of animal models, however, it is interesting to consider that rapamycin — or more sophisticated strategies to inhibit TOR signalling — might prove useful in combating many age-associated disorders. Also, as relevant downstream targets of TOR are better characterized, it may be possible to develop pharmacological strategies that provide the health and longevity benefits without unwanted side effects. So, although extending human lifespan with a pill remains the purview of science-fiction writers for now, the results of Harrison et al.1 provide a reason for optimism that, even during middle age, there's still time to change the road you're on.

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References

1. Harrison, D. E. et al. Nature advance online publication doi:10.1038/nature08221 (2009).
2. Jia, K., Chen, D. & Riddle, D. L. Development 131, 3897–3906 (2004). | Article | PubMed | ISI | ChemPort |
3. Kaeberlein, M. et al. Science 310, 1193–1196 (2005). | Article | PubMed | ISI | ChemPort |
4. Kapahi, P. et al. Curr. Biol. 14, 885–890 (2004). | Article | PubMed | ISI | ChemPort |
5. Powers, R. W. 3rd, Kaeberlein, M., Caldwell, S. D., Kennedy, B. K. & Fields, S. Genes Dev. 20, 174–184 (2006). | Article | PubMed | ISI | ChemPort |
6. Vellai, T. et al. Nature 426, 620 (2003). | Article | PubMed | ISI | ChemPort |
7. Stanfel, M. N., Shamieh, L. S., Kaeberlein, M. & Kennedy, B. K. Biochim. Biophys. Acta advance online publication doi:10.1016/j.bbagen.2009.06.007 (2009).
8. Smith, E. D. et al. Genome Res. 18, 564–570 (2008). | Article | PubMed |
9. Steffen, K. K. et al. Cell 133, 292–302 (2008). | Article | PubMed | ChemPort |
10. Hansen, M. et al. PLoS Genet. 4, e24 (2008). | Article | PubMed | ChemPort |

Turd_Ferguson
7/8/2009, 02:27 PM
Why the **** would I want to be here any longer than I have to?:D

1890MilesToNorman
7/8/2009, 02:28 PM
Damn, now I gotta go make more money to pay for all those extra years of life!

CK Sooner
7/8/2009, 02:31 PM
If these does actually work and makes people age lower than we are going to have to do something close to what China is doing and limit how many children people can have.

Turd_Ferguson
7/8/2009, 02:31 PM
Damn, now I gotta go make more money to pay for all those extra years of life!Why spend all the money when somebody will prolly kill your *** before too long anyway?:D

Collier11
7/8/2009, 02:32 PM
Im not going to risk pissing of GOD, ill stick with whatever he gives me :)

Turd_Ferguson
7/8/2009, 02:34 PM
If these does actually work and makes people age lower than we are going to have to do something close to what China is doing and limit how many children people can have.I say we start with you.

CK Sooner
7/8/2009, 02:35 PM
I say we start with you.

I am already born, asswhipe.

;):D

Jacie
7/8/2009, 02:41 PM
If these does actually work and makes people age lower than we are going to have to do something close to what China is doing and limit how many children people can have.

I believe they have backed off from the policy of one child per couple . . .

CK Sooner
7/8/2009, 02:42 PM
I believe they have backed off from the policy of one child per couple . . .

I wonder if there is still a policy at all then?

Turd_Ferguson
7/8/2009, 02:50 PM
I am already born, asswhipe.

;):DTo bad Dr. Tiller was kilt...we could have him do a really,really,really late term abortion.:D

Collier11
7/8/2009, 02:53 PM
INAPPROPRIATE!












DAMN FUNNY! ;)

TheUnnamedSooner
7/8/2009, 03:31 PM
Yeah, but will it keep me from sh*tting myself when i'm old?

Collier11
7/8/2009, 03:34 PM
dont you already ****e yourself now

The Remnant
7/8/2009, 03:44 PM
I thought EXTENZE already made life longer.

Collier11
7/8/2009, 03:47 PM
I thought EXTENZE already made life longer.

[hairGel] THATS NOT WHAT GETS LONGER!!!

Fraggle145
7/8/2009, 04:33 PM
Well if you get any of your organs replaced you'll probably be on it anyway... just not the same amount.

Maybe they could replace your colon and you wouldnt **** yourself so much?

ndpruitt03
7/8/2009, 05:00 PM
So I can pretty much do what I want but take this pill and live a long miserable life? How fun!

stoopified
7/9/2009, 11:13 PM
I ain't touching that pill if Billy Mayes made an infommercial for it.Not trying to be funny but I have seen health insurance spots hawked by Mayes recently(twice today)and if I'm buying new health insurance,it won't be from a dead man.Same would go for a longevity pill.

RUSH LIMBAUGH is my clone!
7/10/2009, 01:16 AM
So, we can look forward to a longer life, but we will have to endure it with pneumonia and Multiple Sclerosis?

Crucifax Autumn
7/10/2009, 02:37 AM
No, just Obama and Palin!