Jackson Lab, collaborators extend lifespan of aging mice with transplant drug
| Date: July 8, 2009 |
Bar Harbor, Maine -- A drug used by human transplant recipients to prevent rejecting their new organ can significantly extend the lifespan of mice, finds a paper published online this week in Nature.
Rapamycin is a bacterial product originally found in a soil sample from Rapa Nui, or Easter Island. It targets TOR, a kinase that regulates protein translation, cell growth and cell metabolism in response to environmental cues. Reducing TOR function has already been shown to extend the life of yeast, nematode worms and flies, but now Jackson Laboratory Professor David Harrison and colleagues report the effect for the first time in mammals.
The team fed rapamycin to mice late in their life--600 days of age--and showed that the median and maximal lifespan of treated animals was extended by 9 to 14%. Currently, the only way to extend the life of a rodent is by severely restricting its diet, so this marks the first report of a pharmacological intervention that lengthens the life of mammals.
Hear a podcast interview with David Harrison by Kerri Smith of Nature
According to Harrison, the findings are significant for several reasons:
- The mice in the experiment were quite genetically diverse, the progeny of crossing four different strains. So, he says, it's unlikely that life extension comes from merely postponing a few strain-specific diseases.
- The treatment did not start until mice were fairly old; 600 days of age for a mouse is equivalent to about 60 years of age for human beings. No other intervention has been this effective when starting so late in life, on such a diverse population.
- The treatment is targeted to a single enzyme, so its effectiveness is well defined on a biochemical level.
In a related "News & Views" article in the journal Nature, Matt Kaeberlein and Brian Kennedy warn that "healthy individuals should not consider taking rapamycin to slow aging--the potential immunosuppressive effects of this compound alone are sufficient to caution against this." But it's hoped that the finding will lead to the development of interventions for the treatment and prevention of age-related diseases.
The research was conducted as part of the National Institute of Aging's Interventions Testing Program, a multi-institutional project to study a wide variety of substances--including pharmaceuticals, dietary supplements and foods--for their potential to extend lifespan and delay disease and dysfunction in mice. Harrison's collaborators in the Nature report include Richard Miller of the University of Michigan and Randy Strong of the University of Texas Health Sciences Center at San Antonio.
How great was the effect? "Effects can be stated several ways," Harrison says. "Pooling data from all three sites, and expressed as lifespan increase from 600 days of age, males had a 28% increase and females a 38% increase. Expressed as age at 90% mortality, males had an increase of 9% and females of 14%. By comparison, these effects are similar to preventing all atherosclerosis and cancer deaths in humans. This is because incidences of all other causes of death increase exponentially."
The Jackson Laboratory is an independent, nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine, with a facility in Sacramento, Calif. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the biomedical community.
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