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Easter Island Compound Extends Life Of Middle-Aged Mice

Posted on: Wednesday, 8 July 2009, 15:30 CDT

A compound in the soil of Easter Island in the South Pacific significantly extends the lifespan of older mice, researchers at the University of Texas reported on Wednesday.

The molecule, known as "rapamycin" after the island's Polynesian name, Rapa Nui, is a bacterial byproduct discovered in a sample obtained from the remote Pacific archipelago during the 1970s.

The researchers gave the rapamycin to mice that were the human equivalent of 60 years old, and found it expanded lifespans by 28 to 38 percent, enabling some of the mice to live to the human equivalent of 100 years old.

In human terms, this would exceed the predicted increase in lifespan resulting from the cure or prevention of cancer and heart disease, the researchers said.

The research is part of the National Institute on Aging (NIA) Interventions Testing Program, which seeks compounds that might help people remain active and disease-free throughout their lives.

The Texas study was led by scientists at two institutes at the UT Health Science Center: the Institute of Biotechnology (IBT) and the Barshop Institute for Longevity and Aging Studies.  The University of Michigan at Ann Arbor and Jackson Laboratory in Bar Harbor, Maine, are the other two centers involved.

"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 was later used to prevent organ rejection in transplant recipients.  
It is also used in stents for patients during angioplasty to keep coronary arteries open and is in clinical trials for the treatment of cancer.

The aging study found that adding rapamycin to the diet of older mice increased their lifespan. 

"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., director of the NIA-funded Aging Interventions Testing Center in San Antonio.

Dr. Strong is a professor of pharmacology at the UT Health Science Center and a senior research career scientist with the South Texas Veterans Health Care System.

The research has "interesting implications for our understanding of the aging process," said Z. Dave Sharp, Ph.D., director of the Institute of Biotechnology and professor and chairman of the Health Science Center's Department of Molecular Medicine.

"In addition," Dr. Sharp said, "the findings have immediate implications for preventive medicine and human health, in that rapamycin is already in clinical usage."

Aging researchers currently acknowledge just two life-extending interventions in mammals: calorie restriction and genetic manipulation.

Rapamycin appears to partially shut down the same molecular pathway as restricting food intake or reducing growth factors, the study found.  It accomplishes this through a cellular protein known as mTOR (mammalian target of rapamycin), which controls many processes in cell metabolism and stress responses.

Ten years ago, Dr. Sharp proposed to his colleagues that mTOR might be involved in calorie restriction.

"It seemed like an off-the-wall idea at that time," Dr. Richardson said.

In 2004, one year after the launch of the NIA Interventions Testing Program, Dr. Sharp submitted a proposal that rapamycin be studied for its anti-aging effects. The proposal was approved, and testing centers in San Antonio and elsewhere began to include rapamycin in the diets of mice.

The male and female mice were crossbred from four different strains of mice to more closely mimic the genetic diversity and disease susceptibility of the human population.

But Dr. Strong soon found that Rapamycin was not stable enough in food or in the digestive tract to register in the animals' blood level. So he collaborated with the Southwest Research Institute in San Antonio to improve the bioavailability of the compound through a process known as microencapsulation. The reformulated compound 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.

The original goal was to begin feeding the mice at 4 months of age, but due to the delay caused by developing the new formulation the mice were not started until they were 20 months old – the equivalent of 60 years of age in humans.

"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."

"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,” added Dr. Strong.

The study was published Wednesday, July 8, in the journal Nature.

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On the Net:

• University of Texas
• National Institute on Aging
• Nature

Source: redOrbit Staff & Wire Reports

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