Anti-aging study shows drug gives mice longevity boost even late in life

ANN ARBOR, Mich. - A drug known to suppress the immune system, and possibly inhibit cancer and other destructive aging processes, is the new frontrunner in federally supported anti-aging studies.

In the study, mice fed the drug rapamycin, even starting in late middle age, had their lifespan extended by 9 to 14 percent. The results appear online and will be published in the journal Nature July 16.

University of Michigan scientist Richard A. Miller, M.D., Ph.D., says the findings are the most robust yet in the ongoing animal experiments at his lab and two others. The study, now in its sixth year, tests agents that have potential to slow aging. The other study sites are the University of Texas Health Science Center in San Antonio, Texas, and the Jackson Laboratory in Bar Harbor, Maine.
"While other results have been promising, the rapamycin effect is bigger, and worked even when started in late middle age," says Miller, a professor of pathology at the U-M Medical School and associate director for research at the U-M Geriatrics Center. Miller is also a research scientist at the Ann Arbor VA Medical Center.
In the study, both male and female mice who were 600 days old were fed the experimental diet. Mice fed a normal diet with rapamycin lived longer than those fed a normal diet without the drug. Rapamycin led to a 14 percent increase in lifespan in female mice, and a 9 percent increase in lifespan for male mice.
The mice were well past middle age when the study started. Rarely does a mouse of this type live longer than 1,200 days.
In a separate study, rapamycin fed to mice beginning at 270 days of age increased survival in both male and females.
The idea for using rapamycin was suggested by Zelton Dave Sharp, of the University of Texas. A review committee decided to test this agent because rapamycin blocks a protein called "target of rapamycin," or TOR. Mutant worms with low TOR are longer-lived than regular worms.  The TOR also plays a big role in how cells respond to nutrients, hormones and stress.
The anti-aging results present a potential new strength of rapamycin. Rapamycin is a powerful drug that's used in medicine to turn down immune responses, for example in patients who have had a kidney transplant. The drug diminishes the patient's ability to reject the transplanted kidney. It's also emerging as an anti-cancer drug.
"We do not know if the good effects of rapamycin in our mice are due to its anti-immune effects, its anti-cancer effects, or some other effect," Miller says. "We're hoping that we may someday prove that the drug has an anti-aging effect with the ability to slow many aspects of aging."
The large, carefully controlled study at the three sites, called the NIA interventions Testing Program, is intended to provide some of the first reliable data on potential drugs to slow aging and its accompanying ills, he says.
Miller says prior studies of putative anti-aging medications have typically not been repeated at second sites, partly due to time and expense, and their results have proven to be hard to confirm in subsequent studies. "So showing that the drug worked at three sites provides much stronger evidence for effectiveness than a study at any one site would produce
"The observation that the drug worked in all three sites makes the basic finding much less likely to be due to some statistical fluke or some unsuspected experimental factor," Miller says.
Randy Strong of the University of Texas Health Science Center, David E. Harrison of the Jackson Laboratory and Miller are chief collaborators in the National Institute on Aging Project and are authors of the report, along with Sharp, James F. Nelson, Clinton M. Astle, Kevin Flurkey, Nancy L. Nadon, J. Erby Wilkinson, associate professor of comparative pathology in the Department of Laboratory Animal Medicine and associate professor of pathology at the U-M Medical School, Krystyna Frenkel, Christy S. Carter, Marco Pahor, Martin A. Javors, and Elizabeth Fernandez.
Funding: National Institute on Aging, part of the National Institutes of Health
Reference: Nature, DOI: 10.1038/nature 08221; scheduled for print publication July 16, 2009
Written by Shantell M. Kirkendoll 


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