Easter Island Compound Extends Lifespan Of Old Mice: 28 To 38 Percent Longer Life"ScienceDaily (July 9, 2009) — The giant monoliths of Easter Island are worn, but they have endured for centuries. New research suggests that a compound first discovered in the soil of the South Pacific island might help us stand the test of time, too...the Easter Island compound – called "rapamycin" after the island's Polynesian name, Rapa Nui – extended the expected lifespan of middle-aged mice by 28 percent to 38 percent. In human terms, this would be greater than the predicted increase in extra years of life if cancer and heart disease were both cured and prevented...The rapamycin was given to the mice at an age equivalent to 60 years old in humans..."I've been in aging research for 35 years and there have been many so-called 'anti-aging' interventions over those years that were never successful," said Arlan G. Richardson, Ph.D., director of the Barshop Institute. "I never thought we would find an anti-aging pill for people in my lifetime; however, rapamycin shows a great deal of promise to do just that."...Discovered in the 1970s, rapamycin was first noted for its anti-fungal properties and later was used to prevent organ rejection in transplant patients. It also is used in stents, which are implanted in patients during angioplasty to keep coronary arteries open. It is in clinical trials for the treatment of cancer..."We believe this is the first convincing evidence that the aging process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age," said Randy Strong, Ph.D., who directs the NIA-funded Aging Interventions Testing Center in San Antonio...Rapamycin appears to partially shut down the same molecular pathway as restricting food intake or reducing growth factors...It does so through a cellular protein called mTOR (mammalian target of rapamycin), which controls many processes in cell metabolism and responses to stress...In 2004, a year after the launch of the NIA Interventions Testing Program, Dr. Sharp submitted a proposal that rapamycin be studied for anti-aging effects. The proposal was approved, and testing centers in San Antonio and elsewhere began to include rapamycin in the diets of mice...Dr. Strong soon recognized a problem: Rapamycin was not stable enough in food or in the digestive tract to register in the animals' blood level. He worked with the Southwest Research Institute in San Antonio to improve the bioavailability of the compound through a process called microencapsulation. The reformulated drug was stable in the diet fed to the mice and bypassed the stomach to release in the intestine, where it could more reliably enter the bloodstream..."I did not think that it would work because the mice were too old when the treatment was started," Dr. Richardson said. "Most reports indicate that calorie restriction doesn't work when implemented in old animals. The fact that rapamycin increases lifespan in relatively old mice was totally unexpected."...Added Dr. Strong: "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 overall health cost for the U.S. and the world will be enormous."Sirolimus - WikipediaRapamycin extends life in mice, raising hopes of life-prolonging drug for humans - Times Online"Scientists warned, however, that nobody should take rapamycin in the hope of living longer. The drug, originally identified in soil samples from Easter Island, is a powerful suppressor of the immune system, commonly given to patients to help to prevent the rejection of transplanted organs, and its dangers to healthy people would far outweigh any potential benefit...Matt Kaeberlein and Brian Kennedy, of the University of Washington, wrote in a commentary on the work: “Certainly, healthy individuals should not consider taking rapamycin to slow ageing. The potential immunosuppresive effects of this compound are sufficient to caution against this...“It may be possible to develop pharmacological strategies that provide the health and longevity benefits without unwanted side effects.” "Antibiotic Delayed Aging in Mice - NYTimes.com"“It’s no longer irresponsible to say that following these up could lead to medicines that increase human life span by 10, 20 or 30 percent,”"BBC NEWS | Health | Tests raise life extension hopes""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. "What Does a Drug That Extends Life in Mice Mean for Humans? - TIME"Scientists think rapamycin's cellular target — called mTOR for "mammalian target of rapamycin" — helps regulate the body's response to nutrients and may also, according to Strong, "gear up responses to stress," such as the oxidative stress that damages proteins and DNA and contributes to disease development. "What we're doing with rapamycin," Strong says, "is we're actually tricking the cells into thinking that they're depleted of nutrients. Rather than the animals losing weight — we haven't noticed any weight loss — they may be just using their proteins more efficiently, and then repairing proteins more efficiently...It's this cellular efficiency, perhaps, that delays aging and helps preserve animals' good health. The findings suggest that rapamycin does not affect or prevent any one disease specifically — the mice in the study died of various causes, with no real difference between mice that received rapamycin and those that didn't — but rather that it slows aging overall...Rapamycin's life-extending effect has been demonstrated by other researchers in past studies of worms, fruit flies and yeast; the drug appears to interfere with a similar cellular process in those species too. "I think this is a big leap from those invertebrate species to mammals," says Strong, who is also a senior research scientist for Veteran Affairs. "This gives us a good idea that perhaps it would work in humans too."...Earlier human trials have shown, however, that rapamycin can have serious side effects. Because it is an immune suppressant, it can make users susceptible to opportunistic infections. It has also been linked to hyperlipidemia, or high levels of triglycerides in the blood, which can lead to heart disease. It's unclear whether these problems would counteract any longevity benefit that rapamycin might provide in humans. Says Strong, "I think more immediately, people are starting to look at [rapamycin] for age-related diseases like Alzheimer's disease, Parkinson's disease or kidney disease." The drug has also recently entered clinical trials as a human cancer treatment, while another study published last year showed that it may reverse mental retardation caused by the genetic disease tuberous sclerosis in mice..."Two Mammals' Longevity Boosted - WSJ.com:
"'It's time to break out of our denial about aging,' said Aubrey de Grey, a British gerontologist who has drawn controversy for his suggestions on how to forestall death. 'Aging is, unequivocally, the major cause of death in the industrialized world and a perfectly legitimate target of medical intervention.'...The studies boost the notion that restricting metabolic activity -- whether through a drug or calorie restriction, which involves sharply reducing food intake -- lengthens life span...A Wyeth spokesman called it an "interesting preclinical study" and said Wyeth just became aware of the finding Wednesday..."Hmmm, Wyeth asleep at the wheel? Doesn't inspire confidence in the company.
Secret to a longer life lies on Easter Island - Science, News - The Independent:
"Originally developed as an anti-fungal agent, rapamycin was soon found to have powerful immuno-suppressant properties and thus be valuable for preventing rejection of transplanted organs. It was also found to delay the ageing process when used experimentally with three sets of lower organisms: yeast, nematode worms and fruit flies...Also known as sirolimus, rapamycin was first discovered as a product of the bacterium Streptomyces hygroscopicus, which was found in an Easter Island soil sample..."Cancer Drug Delays Aging in Mice | Wired Science | Wired.com:
"Gerontology itself is a youthful field, its progress having been slowed by aging’s daunting complexity and a tendency among scientists and doctors to consider diseases as entirely separate, rather than as manifestations of a common origin. But in recent years, that thinking has started to change. From diabetes to cancer to dementia, many diseases become steadily more likely with advancing age. Their common risk profile hints at common origins...“There’s no obvious way to turn this into a lifespan extension for humans,” said David Sinclair, a Harvard gerontologist not involved in this study. “But it’s clearly a milestone in the field, to be able to use one small molecule to have such a big effect in an animal. Twenty years ago, if you suggested that one small molecule could slow down aging, people would have said it was impossible.”... More than 1,900 mice, their total genetic variation roughly comparable to that found in humans, were fed rapamycin. Treatment starting when they were around 20 months old, a stage comparable to early old age in people...The average date at which 90 percent of the mice were dead — a convenient metric for quantifying lifespan — rose from 1,078 days to 1,179 days in males, and from 1,094 days to 1,245 days in females. In proportional terms, old age lasted one-quarter longer than expected for males, and two-fifths longer for females.
When tested on nine-month-old mice, rapamycin had little effect. “It’s possible that for some agents, the most beneficial effect will only start late in life,” said Harrison."...Steven Austad, a University of Texas gerontologist who has been skeptical about resveratrol’s apparent longevity-enhancing effects, called the results “particularly significant.” He said the multi-center study design gave them “instant credibility...Some evidence suggests that mTOR’s pathway shares many functions and genes with the sirtuin pathway targeted by resveratrol. The extent of the overlap is unclear, but both appear to be involved in processes affected by caloric restriction...“There are only a handful of really crucial pathways that control lifespan,” said Sinclair. “These pathways all talk to each other. You can think of them not as separate, but as part of a larger network of pathways that are communicating and working in concert.”
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