HSC scientists discover mice live longer with rapamycin
SAN ANTONIO (July 8, 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 University of Texas Health Science Center at San Antonio and two collaborating centers reported in the July 8 edition of the journal Nature that the compound rapamycin, named after the island's Polynesian name Rapa Nui, has extended the expected lifespan of middle-aged mice by 28 percent to 38 percent. In human terms, this would be greater than the predicted life expectancy if cancer and heart disease were both cured and prevented.
The studies are part of the National Institute on Aging (NIA) Interventions Testing Program, which seeks compounds that might help people live active and disease-free lives into old age. The University of Michigan at Ann Arbor and the Jackson Laboratory in Bar Harbor, Maine, were also involved in the study.
The Texas study was led by scientists at two UT Health Science Center institutes — the Institute of Biotechnology (IBT) and the Barshop Institute for Longevity and Aging Studies.
"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. It has been used to prevent organ rejection in transplant patients and in stents implanted during angioplasty to keep coronary arteries open. The compound also is in clinical trials for the treatment of cancer.
The experiments on aging found that adding rapamycin to the diet of older mice increased their lifespan. The results were the same in Texas, Michigan and Maine.
“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. He 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.
Researchers have said that there are only two ways to extend life in mammals: calorie restriction and genetic manipulation. Rapamycin appears to extend life through a cellular protein called mTOR (mammalian target of rapamycin), which controls many processes in cell metabolism and responses to stress.
A decade ago, IBC Director Z. Dave Sharp, Ph.D., professor and chairman of the Health Science Center’s Department of Molecular Medicine, proposed that mTOR might be involved in calorie restriction. In 2004, he submitted a proposal that rapamycin be studied for anti-aging effects. Although it was an unusual proposition, it was approved and testing of rapamycin in the diets of mice began at the three study centers.
There was a problem, however, in that rapamycin was not stable enough in food or in the digestive tract to register in the animals’ blood level. Dr. Strong worked with 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.
The original goal was to begin feeding the mice when they were 4 months old, but because of the technical delay, the study could not start until the mice were 20 months old — the equivalent of 60 years of age in humans.
“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,” Dr. Richardson said.
Dr. Strong added, “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 it work as envisioned, the potential reduction in overall health cost for the U.S. and the world will be enormous.”
Richard Miller, M.D., Ph.D., was principal investigator of the study at the University of Michigan and David Harrison, Ph.D., led the study at the Jackson Laboratory.
The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $16.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $36 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 26,400 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields. For more information, visit www.uthscsa.edu.
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