A new study by Dr. Yiqiang Zhang and colleagues of the Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio, has found that mice fed the drug rapamycin as part of their diet starting when they were 19 months old (roughly equivalent to 60 human years of age) had lifespan increases more modest than in some previous studies. Compared to untreated mice, the lifespan of the treated rodents increased by an average of about 3 percent, or 7 percent for mice who had lived to older age already.
Researchers hope rapamycin may also serve to prolong life and ward off aging-related diseases in people, especially as it’s already tested and approved for another human use: to prevent transplant rejection. Rapamycin is a naturally-occurring bacterial agent first isolated in the 1970s from soil taken from isolated Easter Island in the South Pacific Ocean, and first noted for its anti-fungal properties. Subsequently the base drug was federally approved to suppress organ rejection in transplant recipients. The name, “rapamycin,” derives from the island’s Polynesian name, “Rapa Nui.”
A World Science report says that rapamycin, may also be effective in prolonging life and warding off aging-related diseases in humans, especially since it’s already been tested and approved for another human use: to prevent transplant rejection. However, the article notes that obstacles remain before human use of rapamycin as a human longevity booster can be approved.
A study published in Science 30 March 2012 (30 March 2012: Vol. 335 no. 6076 pp. 1578-1579 , DOI: 10.1126/science.1221365) entitled “Rapamycin Paradox Resolved” by Katherine J. Hughes and Brian K. Kennedy of the Buck Institute for Research on Aging at Novato, California, notes that in 2009, rapamycin was the first drug reported to extend the life span of mice — roughly 15% in females and 10% in males. However, Drs. Hughes and Kennedy caution that a problem regarding rapamycin’s use (or that of rapalog derivatives) to extend healthspan is that it causes glucose intolerance and insulin resistance in mice and humans, effects of which could outweigh any longevity benefits. However, they reference research by Dudley W. Lamming et al. reported in the same issue of Science, entitled “Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity” (Science 30 March 2012: Vol. 335 no. 6076 pp. 1638-1643, DOI: 10.1126/science.1215135) that has identified a mechanism by which the drug confers insulin resistance, and shows that rapamycin’s effect on glucose homeostasis and longevity can be uncoupled.
At year end 2009, Science, Nature and TIME magazine all reported that rapamycin, an antibiotic used in transplant patients, had been shown to extend the lifespan of aged mice and was among the most significant and exciting scientific breakthroughs of the year. Science, in an article called “Live Long and Prosper,” named the rapamycin study as a runner-up for Breakthrough of the Year. Nature included a science writer’s article about the study in its Reader’s Choice Top 10 feature. TIME mentioned the research in The Year in Health 2009.
The idea to test rapamycin on mouse longevity came from Z. Dave Sharp, Ph.D., professor of molecular medicine at the Health Science Center. In October, Dr. Sharp accepted a prestigious Mprize Lifespan Achievement Award in New York City from the Methuselah Foundation in recognition of his pioneering effort to study the effect of rapamycin on aging in mice.
A UTHSC release notes Dr. Sharp proposed that since rapamycin is the first pharmaceutical intervention to successfully extend life span of lab mice, a rapamycin study to the National Institute on Aging Interventions Testing Program (ITP), which seeks compounds that might help people remain active and disease-free throughout their lives would be appropriate.
Randy Strong, Ph.D., professor of pharmacology in the School of Medicine at the Health Science Center, led the research study under the National Institute on Aging Interventions Testing Program. Investigators at three U.S. sites – UT Health Science Center’s Barshop Institute for Longevity and Aging Studies; the University of Michigan at Ann Arbor; and Jackson Laboratory in Bar Harbor, Maine; worked independently. Dr. Strong led a team at the Barshop Institute. In the study, reported in July, 2009 in the journal Nature, the base drug proved to be the first pharmaceutical intervention to successfully extend life span in laboratory mice, extending the expected lifespan of middle-aged mice by 28 percent to 38 percent, and noting that 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 2009 research finding that adding rapamycin to the diet of older mice increased their lifespans, produced similar results repeated by researchers in Texas, Michigan and Maine.
A significant obstacle to implementing the rapamycin intervention in mice was that the drug is easily degraded in their food and was not suitable for chronic studies. He worked with Southwest Research Institute to devise a microencapsulated form of the compound that resists degradation in the mouse chow. This made it possible to carry out the study.
In 2010, Veronica Galvan, Ph.D., assistant professor of physiology at the Barshop Institute, and Salvatore Oddo, Ph.D., assistant professor of physiology, reported that the base drug rescued learning and memory in two entirely different mouse models of Alzheimer’s disease.
The ability of rapamycin-related drugs to potentially slow the aging process as suggested in the animal experiments at The University of Texas Health Science Center San Antonio like the ones cited above, and others, led to establishment of a new biotech company, Rapamycin Holdings Inc., which is licensing exclusive rights to intellectual property central to several aspects of the rapamycin-related drugs, and which hopes to exploit new commercial possibilities for rapamycin. The company has announced that since 2010 it has been working to advance commercialization of products stemming from the patent pending technology developed by the Health Science Center researchers, and that more clinical trials will yield the next preclinical results by mid-year 2013, and advance Phase 1 trials shortly thereafter.
Rapamycin Holdings will be looking to raise an additional $6 million as it approaches the point of taking its first drug product to Phase 1 clinical trials.
On December 7, 2012, Rapamycin Holdings Chief Executive Officer George Fillis announced that the company has acquired those exclusive rights from the UT Health Science Center and its collaborator, Southwest Research Institute. Rapamycin Holdings signed the license agreement with STTM, a multi-institution University of Texas technology-management office operated by the Health Science Center.
Randy Strong, Ph.D., professor of pharmacology in the School of Medicine at the Health Science Center, led a pivotal research study under the National Institute on Aging Interventions Testing Program. Investigators at three U.S. sites worked independently, including Dr. Strong and a team at the Health Science Center’s Barshop Institute for Longevity and Aging Studies, located in the Texas Research Park. In the study, reported in Nature in 2009, the base drug proved to be the first pharmaceutical intervention to successfully extend life span in laboratory mice.
You can check out a UTHSCSA Barshop Institute Rapamycin Profile in which scientists at the Barshop Institute speak on the exciting scientific breakthroughs from studies of rapamycin in aging research in this Youtube video presentation:
The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving federal funding. Research and other sponsored program activity totaled $231 million in fiscal year 2011. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced approximately 28,000 graduates. The $736 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the UTHSC, visit http://www.uthscsa.edu
The Barshop Institute for Longevity and Aging Studies is dedicated to the promotion of healthy aging for everyone. Its world-class scientific community of researchers and physicians seek discoveries to treat and ameliorate the underlying causes of aging, a cost-effective approach to broadly enhance the quality of later life. Explore http://www.barshop.uthscsa.edu to learn about the work of this community of researchers and physicians.