A drug used to prevent the rejection of transplanted organs and as an experimental cancer treatment in humans can significantly increase lifespan when given to adult mice, researchers have found. Mice that were administered the immunosuppressant rapamycin lived an average of 9-14% longer than mice that were not fed the drug, according to a paper published online in Nature today (July 8th).

"Four times a mouse" by Jacques de Gheyn Image: Wikimedia

"This is pretty remarkable," Panjak Kapahi, a geneticist at the Buck Institute for Age Research in California told The Scientist. "There might be more to gain in understanding the downstream effects, but this is already a wonderful start." Kapahi, who was not involved with the study, added that, though preliminary, the finding opens the door for further research into the drug's use for an anti-aging intervention in humans. "It should be applicable to humans, I think."

David Harrison, a gerontologist at The Jackson Laboratory in Bar Harbor Maine and lead author on the paper, told The Scientist that 9%, though seemingly a modest life span increase, is significant when compared to the effect of eradicating some of the most common age-related diseases in humans. "If you prevented all deaths from cancer and atherosclerosis," Harrison said, "it would be a little less than that."

Rapamycin works by inhibiting the target of rapamycin (TOR) signaling pathway, which plays a role in the translating mRNA into proteins and inhibits processes that degrade cellular waste. The drug has been found to extend the life spans of yeast, fruit flies, and nematodes. "This is really the first demonstration that inhibiting TOR also increases lifespan in mammals," said Matt Kaeberlein, a pathologist at the University of Washington in Seattle who was not involved with the study.

Kapahi, who discovered in 2004 that the TOR pathway played a role in extending the life spans of fruit flies, said that Harrison's study is both a "great victory for the invertebrate models of aging," and a fruitful way forward to investigate a potential anti-aging treatment in humans. "You would put your money on a pathway that you know has worked in four different organisms," he said. "This is as good as it gets."

As rapamycin has previously been shown to increase the life spans of invertebrate model organisms, its effect in mice is not entirely surprising, according to Kaeberlein, who wrote a commentary that accompanies the Nature paper. More surprising is the fact that the longer-lived mice in the study were not given rapamycin until they were 600 days old. "That is very surprising to myself and to a lot of people," Kaeberlein told The Scientist. "And it's a very important result." A 600-day-old mouse is roughly equivalent to a human that is 60 years of age, and other successful anti-aging interventions have not proved effective so late in an organism's life.

Kaeberlein said that rapamycin's effectiveness in middle aged mice represents an interesting therapeutic opportunity in humans, because "almost everything that has been found to significantly increase lifespan in model organisms leads to some sort of fitness costs" -- usually by stunting growth or reducing reproductive capacity. A rapamycin-based anti-aging pill administered later in life might circumvent these problems.

Harrison agreed. "It's certainly possible that there may be optimal times to start things when you're old that might be deleterious when you're young," he said. But he joined Kaeberlein and Kapahi in cautioning that the findings should not be interpreted as an invitation for age-conscious humans to ingest the drug. "It's not time to start popping rapamycin for anti-aging," Harrison said, adding that taking rapamycin likely carries significant risks common to other immune suppressants or immunocompromising diseases.

Several questions surrounding the results and rapamycin's impact on the TOR pathway and aging remain to be answered. "What's happening in these animals that are given rapamycin and are living a long time?" asked Kaeberlein. "That's going to be important for the next set of experiments to look at."

Harrison said that he and other researchers collaborating in the National Institute on Aging's Interventions Testing Program are examining the drug's cellular effects and testing a suit of other compounds suspected to increase the longevity of mammals. The effect of rapamycin and the indication that the TOR pathway is important in mammalian aging is a major step towards developing a drug that might prolong human life, he said. "I think this makes us a lot closer than we were before," he said. "Who knows what's going to work, but we have a point here that's ever so much more specific and interesting than we had to start with."


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