Easter Island compound extends lifespan of old mice

Jul 08, 2009
These Easter Island monoliths have endured for centuries. New research suggests that a compound first discovered in soil of the remote South Pacific island might help humans stand the test of time, too. Credit: Image copyright Happy Alex, 2009. Used under license from shutterstock.com

The giant monoliths of Easter Island are worn, but they have endured for centuries. New research suggests that a compound first discovered in the soil of the South Pacific island might help us stand the test of time, too.

Wednesday, July 8, in the journal Nature, The University of Texas Health Science Center at San Antonio and two collaborating centers reported that the Easter Island compound - called "rapamycin" after the island's Polynesian name, Rapa Nui - extended the expected lifespan of middle-aged mice by 28 percent to 38 percent. In human terms, this would be greater than the predicted increase in extra years of life if cancer and heart disease were both cured and prevented.

The rapamycin was given to the mice at an age equivalent to 60 years old in humans.

The studies are part of the National Institute on Aging (NIA) Interventions Testing Program, which seeks compounds that might help people remain active and disease-free throughout their lives. The other two centers involved are the University of Michigan at Ann Arbor and Jackson Laboratory in Bar Harbor, Maine.

The Texas study was led by scientists at two institutes at the UT Health Science Center: the Institute of Biotechnology (IBT) and the Barshop Institute for Longevity and Aging Studies.

"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," said Arlan G. Richardson, Ph.D., director of the Barshop Institute. "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."

Versatile compound

Discovered in the 1970s, rapamycin was first noted for its anti-fungal properties and later was used to prevent in transplant patients. It also is used in stents, which are implanted in patients during angioplasty to keep coronary arteries open. It is in clinical trials for the treatment of cancer.

The new aging experiments found that adding rapamycin to the diet of older mice increased their lifespan. The results were the same in Texas, Michigan and Maine.

"We believe this is the first convincing evidence that the aging process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age," said Randy Strong, Ph.D., who directs the NIA-funded Aging Interventions Testing Center in San Antonio. He is a professor of pharmacology at the UT Health Science Center and a senior research career scientist with the South Texas Veterans Health Care System.

The findings have "interesting implications for our understanding of the aging process," said Z. Dave Sharp, Ph.D., director of the Institute of Biotechnology and professor and chairman of the Health Science Center's Department of Molecular Medicine.

"In addition," Dr. Sharp said, "the findings have immediate implications for preventive medicine and human health, in that rapamycin is already in clinical usage."

Molecular pathway

Aging researchers currently acknowledge only two life-extending interventions in mammals: calorie restriction and genetic manipulation. Rapamycin appears to partially shut down the same molecular pathway as restricting food intake or reducing growth factors.

It does so through a cellular protein called mTOR (mammalian target of rapamycin), which controls many processes in cell metabolism and responses to stress.

A decade ago, Dr. Sharp proposed to his colleagues that mTOR might be involved in calorie restriction. "It seemed like an off-the-wall idea at that time," Dr. Richardson said.

In 2004, a year after the launch of the NIA Interventions Testing Program, Dr. Sharp submitted a proposal that rapamycin be studied for anti-aging effects. The proposal was approved, and testing centers in San Antonio and elsewhere began to include rapamycin in the diets of mice.

The male and female mice were cross-bred from four different strains of mice to more closely mimic the genetic diversity and disease susceptibility of the human population.

Dr. Strong soon recognized a problem: Rapamycin was not stable enough in food or in the digestive tract to register in the animals' blood level. He worked with the Southwest Research Institute in San Antonio to improve the bioavailability of the compound through a process called microencapsulation. The reformulated drug was stable in the diet fed to the mice and bypassed the stomach to release in the intestine, where it could more reliably enter the bloodstream.

Older mice

The original goal was to begin feeding the mice at 4 months of age, but because of the delay caused by developing the new formulation, the mice were not started until they were 20 months old - the equivalent of 60 years of age in humans.
The teams decided to try the rapamycin intervention anyway.

"I did not think that it would work because the mice were too old when the treatment was started," Dr. Richardson said. "Most reports indicate that calorie restriction doesn't work when implemented in old animals. The fact that rapamycin increases lifespan in relatively old was totally unexpected."

Added Dr. Strong: "This study has clearly identified a potential therapeutic target for the development of drugs aimed at preventing age-related diseases and extending healthy lifespan. If rapamycin, or drugs like rapamycin, works as envisioned, the potential reduction in overall health cost for the U.S. and the world will be enormous."

Source: University of Texas Health Science Center at San Antonio

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User comments : 15

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gmurphy
4.8 / 5 (6) Jul 08, 2009
brilliant, it was only a matter of time before something like this came along, and once we've got a toe hold on this sort of life extension tech, the whole industry will open up. I do not want to grow old and die. Ethical ramifications of biological immortality can go and get f**ked, I like being alive
NeilFarbstein
3.3 / 5 (3) Jul 08, 2009
Me too. If they give the same dose to humans will it cause an immune disorder? Maybe it can be combined with SIRT stimulators
PinkElephant
5 / 5 (3) Jul 09, 2009
Reminds me of something from the opening lines of movie "Dune":

In this time, the most precious substance in the universe is the spice Melange. The spice extends life, the spice expands consciousness, the spice is vital to space travel.


Well, ok, so we only have 1 out of 3... SO FAR... :-P
COOLTYCHO
5 / 5 (2) Jul 09, 2009
We should totally pump this chemical into the earth's air so we can breath it in 24/7 and turn into those big floating Navigators from Dune!

http://images2.wi...ovie.jpg
Myria83
5 / 5 (2) Jul 09, 2009
Could it be the discovery of the Holy Graal...?
I'll stay tuned, waiting for trials on humans.
Doug_Huffman
not rated yet Jul 09, 2009
El_Nose
5 / 5 (2) Jul 09, 2009
i wonder what the effect of Rapamycin and resveratrol or other polyphenols have on aging in combination.

"I would like to live a thousand years or so but barring that a few hundred would be nice" -- CEO CEO Nwabudike Morgan
El_Nose
not rated yet Jul 09, 2009
ahh --- pumping a immune system suppressant into the atmosphere would be a bad bad thing.
tkjtkj
3 / 5 (2) Jul 09, 2009
"If rapamycin, or drugs like rapamycin, works as envisioned, the potential reduction in overall health cost for the U.S. and the world will be enormous."

Or, if the course of events prior to a very elderly person's ultimate death include 3 times as long to die after many more years of being nursed in a debilitated state, the costs could be truly enormous. And I thought 'Medicare' was insolvent NOW! ..
Ethelred
5 / 5 (1) Jul 09, 2009
After looking at the link Doug posted I have to think that this drug is not going to be used, as is, for anti-aging. Its immunosupressant effects are bound to have pretty severe consequences in the real world.

Sirolimus inhibits the response to interleukin-2 (IL-2) and thereby blocks activation of T- and B-cells. In contrast, tacrolimus inhibits the production of IL-2.


As with all immunosuppressive medications, rapamycin decreases the body's inherent anti-cancer activity and allows some cancers which would have been naturally destroyed to proliferate. Patients on immunosuppressive medications have a 10- to 100-fold increased risk of cancer compared to the general population. Furthermore, people who currently have or have already been treated for cancer have a higher rate of tumor progression and recurrence than patients with an intact immune system.


So it will need to modified a bit.

Ethelred
Edylc
5 / 5 (2) Jul 09, 2009
These articles make me happy.
I can't wait until life is like a crazy sci-fi movie.
SpaceManSpiff
4.5 / 5 (2) Jul 10, 2009
"While the mice in the study were protected in the laboratory, people taking rapamycin are very susceptible to life-threatening infections and cancers, and require constant medical supervision" - http://www.techno...4/page1/
Nartoon
2.3 / 5 (3) Jul 10, 2009
I plan to live forever,
so far so good!
thorn
5 / 5 (1) Jul 12, 2009
Were are all the super old people who built those statues then?
Andrux
5 / 5 (1) Jul 12, 2009
This could give us the possibility to develop our culture at a much faster rate. Imagine if someone like Albert Einstein could have lived over 150y old. If i had that possibility i would love to get a shot at different careers in one lifetime. Physicist/Biologist/Anthropologist. how fulfilling that would be. Plus, a more diverse knowledge for one person would provide us with a less biased opinion on certain subjects, like medicine for example.