[ExI] Fwd: Rapamycin Extends Lifespan Of Old Mice: 28 To 38 Percent

[hkhenson]

This is impressive.

Keith

>Resent-From: cryonet-list at cryonet.org
>
>CryoNet - Fri 10 Jul 2009
>
>[Note: A special more bioavailable microencapsulated form of 
>rapamycin was used.]
>
>http://www.uthscsa.edu/hscnews/singleformat.asp?newID=3138
>
>Easter Island compound extends lifespan of old mice, scientists 
>report in Nature
>
>Posted: Wednesday, July 08, 2009
>Contact: Will Sansom, (210) 567-2579
>
>UT Health Science Center, other centers reach same result: 28%-38% longer life
>
>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.
>
>Today in the journal Nature, The University of Texas Health Science 
>Center at San Antonio and two collaborating centers reported that 
>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.
>
>The studies are 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 
>other two centers involved are the University of Michigan at Ann 
>Arbor and Jackson Laboratory in Bar Harbor, Maine.
>
>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.
>
>"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."
>
>Versatile compound
>
>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.
>
>The new aging experiments 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.
>
>The findings have "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."
>
>Molecular pathway
>
>Aging researchers currently acknowledge only 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.
>
>It does so through a cellular protein called mTOR (mammalian target 
>of rapamycin), which controls many processes in cell metabolism and 
>responses to stress.
>
>A decade 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, 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.
>
>The male and female mice were cross-bred from four different strains 
>of mice to more closely mimic the genetic diversity and disease 
>susceptibility of the human population.
>
>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.
>
>Older mice
>
>The original goal was to begin feeding the mice at 4 months of age, 
>but because of 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.
>
>The teams decided to try the rapamycin intervention anyway.
>
>"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."
>
>Leaders of the other interventions testing centers are Richard 
>Miller, M.D., Ph.D., of the University of Michigan and David 
>Harrison, Ph.D., at the Jackson Laboratories.