Health InsuranceMiddle-Aged Mice Fed Antibiotic Lived Longer
US researchers found that feeding middle-aged mice the antibiotic rapamycin, an anti-fungal agent originally discovered in the soil of Easter
Island, helped them live between 9 and 14 per cent longer than equivalent mice not fed the drug, which among other things is currently used to
suppress immune systems in transplant patients.
The finding was the result of collaboration among three research centers in the US that are studying the biology of aging, and was published online on
8 July in the journal Nature.
The research centers involved are the University of Texas (UT) Health Science Center at San Antonio, the University of Michigan at Ann Arbor and
Jackson Laboratory in Bar Harbor, Maine. All three centers did the research independently and had the same result.
"Rapamycin" is named after Easter Island"s Polynesian name, Rapa Nui. The increased lifespan in the mice would be the equivalent increase in
life expectancy that would result in humans if cancer and heart disease were cured and prevented, said UT researchers in a press statement. The mice
were given the drug at the human equivalent of age 60.
The study is one of several in the National Institute on Aging (NIA) Interventions Testing Program which is looking for compounds that might help to
keep people active and free of disease for their whole lives.
Dr Arlan G. Richardson, Director of the Barshop Institute for Longevity and Aging Studies at UT Health Science Center, one of the institutes at UT
involved in the study, said:
"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."
"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," he
added.
First discovered in the 1970s, in the soil of Easter Island in the Pacific, rapamycin is an antifungal compound secreted by bacteria. It is used as an
immunosuppressant to stop donated organ rejection in transplant patients, particularly those receiving kidneys, and it is also used in stents that are
implanted in patients who undergo angioplasty to prop open arteries.
The compound is also undergoing clinical trials for the treatment of cancer.
Another of the UT institutes involved in the research is the Institute of Biotechnology. Their director, Dr Z. Dave Sharp, was one of the authors of the
paper, and also chairs UT Health Science Center"s Department of Molecular Medicine.
He told the press that their findings have "interesting implications for our understanding of the aging process," and "immediate implications for
preventive medicine and human health, in that rapamycin is already in clinical usage".
There are two main areas of investigation in anti-aging research at present: calorie restriction and gene manipulation. The researchers suggest that
rapamycin belongs in the first one because it appears to partially shut down the same molucular pathway as restricting food intake.
The pathway is the one controlled by a protein call mTOR (mammalian target of rapamycin) which helps to regulate cell metabolism and stress
responses.
Previous studies have shown that inhibiting the TOR pathway in invertebrates, such as yeast, nematodes and fruitflies extends lifespan, but until now
nobody had investigated the mammalian equivalent.
Sharp first had the idea that mTOR might be involved in calorie restriction about 10 years ago, but it wasn"t until 2004, after the launch of NIA
Program, that he submitted a proposal to study rapamycin for its potential anti-aging effects.
For the study, the researchers used male and female mice that had been cross-bred from 4 different strains so they closely reflected a genetic diversity
and disease susceptibility similar to that of humans.
At first they couldn"t detect the rapamycin in the animals" blood because it was not stable enough to survive in the digestive tract. So with colleagues
from another research center they developed a microencapsulated version of the compound to increase its bioavailability. This helped the compound
remain stable in the gut and pass into the bloodstream.
Their original aim was to start feeding the specially bred mice when they were 4 months old, but because of the delay with the microencapsulation,
they mice were 20 months old by the time the drug was ready, the equivalent of 60 years old in human terms. So the researchers went ahead
anyway.
They wrote that:
"On the basis of age at 90 per cent mortality, rapamycin led to an increase of 14 per cent for females and 9 per cent for males."
Richardson said he did not think it would work because the mice were too old when they started the treatment.
"Most reports indicate that calorie restriction doesn"t work when implemented in old animals," he explained, adding that:
"The fact that rapamycin increases lifespan in relatively old mice was totally unexpected."
The authors suggested that:
"Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both."
Strong said the study has found a potential therapeutic target for future drugs that prevent age-related diseases and extend healthy lifespan.
"If rapamycin, or drugs like rapamycin, works as envisioned, the potential reduction in overall health cost for the US and the world will be enormous,"
he added.
"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice."
David E. Harrison, Randy Strong, Zelton Dave Sharp, James F. Nelson, Clinton M. Astle, Kevin Flurkey, Nancy L. Nadon, J. Erby Wilkinson,
Krystyna Frenkel, Christy S. Carter, Marco Pahor, Martin A. Javors, Elizabeth Fernandez and Richard A. Miller.
Nature Published online
8 July 2009.
doi:10.1038/nature08221
University of Texas Health Science Center at San Antonio.
Written by: Catharine Paddock, PhD
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