Move over, Moai. Easter Island may now boast another odd claim to fame: a midlife longevity drug. In a new study, researchers report that an antibiotic called rapamycin--after the island's Polynesian name, Rapa Nui--enabled middle-aged mice to live up to 16% longer than their rapa-free counterparts. The discovery marks the first time a drug has been shown to lengthen life span in mammals, even when administered late in life.
Scientists first stumbled on rapamycin in soil samples taken from Easter Island in 1965. A bacterium found in the soil, Streptomyces hygroscopicus, secreted the stuff to fend off its bacterial and fungal rivals. Rapamycin has since been used to prevent organ rejection in transplant patients and, most recently, as an antitumor drug. The compound works by inhibiting mTOR, a protein that regulates cell growth and survival. When researchers realized that calorie restriction, which is known to lengthen life spans in mice, also suppresses mTOR activity, they began to wonder if rapamycin might boost longevity as well.
Encouraged by earlier studies showing that insects and worms live longer on rapamycin, a trio of labs--the University of Texas Health Science Center at San Antonio; the University of Michigan, Ann Arbor; and the Jackson Laboratory in Bar Harbor, Maine--decided to test the compound on mice. The labs had access to hundreds of mice genetically diverse enough to model human diversity, thanks to the U.S. National Institute on Aging's Interventions Testing Program, which investigates treatments with life-extending potential.
Pharmacologist Randy Strong and molecular biologist Z. David Sharp, who headed the study's Texas arm, planned to feed young mice rapamycin and observe the drug's effects as they aged. But by the time the researchers formulated a feed that made the rapamycin stable and easily digestible, the mice had grown old--20 months old, or about 60 human years. Because calorie restriction and other life-lengthening measures work best when started young, Strong and his colleagues didn't expect the experiment to work in midlife. Yet the mice lived 28% to 38% longer than the controls from that point on, the researchers report in Nature, the equivalent of 6 to 9 extra years in humans. Their overall life expectancy rose 5% to 16%.
"We were really excited because this appears to be the first drug that slows aging even if it's started later in life," says Strong. Although he and his colleagues aren't yet sure how rapamycin lengthens life, it's thought that suppressing mTOR, whatever the method, prompts the body to hunker down and wait for better times, slowing its growth processes and strengthening its defenses against cell-damaging stressors.
The study comes as "a pleasant surprise," says University of Washington, Seattle, molecular biologist Matthew Kaeberlein, who was among the first to propose the mTOR-longevity link. "This tells us the [mTOR] pathway affects aging in mammals ... and probably affects people as well."
Don't expect antiaging drugs to hit the market anytime soon, though. Rapamycin is known to raise cholesterol levels and, as a potent immune system suppressant, the compound could make its consumers more susceptible to infections. Kaeberlein hopes future studies will measure the health of rapa-enhanced mice and the effects of varying rapamycin doses, in hopes of divorcing the drug's benefits from its dangers.