Could Compound that Extends Lifespan of Mice Have Us
on Track to Real Anti-Aging Pill?
Easter Island compound, rapamycin, extends life of
old mice by almost 40%
(People warned to not start taking the
drug in hopes of extending their own life spans - see
second story
below)
July 10, 2009 The lifespan of old mice was
extended by almost 40 percent by a compound called rapamycin, after
the Polynesian name Rapa Nui for Easter Island, where the compound
was discovered. Interestingly, the rapamycin was given to the mice at an
age equivalent to 60 years old in humans, making it one of the few
anti-aging methods with a chance to work on senior citizens.
The rapamycin 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.
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Aging News & Information |
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The report on the research by the University of
Texas Health Science Center at San Antonio and two collaborating centers
is published in the July 8 issue of the journal Nature.
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 organ
rejection 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 mice 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."
Leaders of the other interventions testing centers
are Richard Miller, M.D., Ph.D., of the University of Michigan and David
Harrison, Ph.D., at the Jackson Laboratories.
Longevity pill on the horizon?
People warned to not start taking the drug in hopes
of extending their own life spans
|
Editors Note: This article is from
7thSpace.com, July 10, 2009. For the original report and updates,
click here. |
While applauding findings that an Easter Island
compound extends the lives of middle-aged mice, University of Washington
(UW) longevity researchers caution that healthy people shouldn't start
taking the drug in the hopes of extending their own life spans -- at
least not yet.
UW scientists Dr. Matt Kaeberlein, assistant
professor of pathology, and Dr. Brian Kennedy, associate professor of
biochemistry, study factors that control aging. They were asked by
Nature to write a commentary on a paper published in the July 9 issue
showing that dietary supplementation with rapamycin increases the life
span of mice.
They observed that, until recently, compounds that
slow the hands of time were in the realm of science fiction, but with
this finding may be closer to reality.
"The possibility that such compounds might exist,
and might perhaps even be within reach," they wrote, "has gained
scientific credibility."
Their News & Views editorial, "Ageing: A Mid-Life
Longevity Drug?" noted that the study, co-led by Dr. David Harrison at
the Jackson Laboratories in Maine, Dr. Richard Miller at the University
of Michigan, and Dr. Randy Strong at the University of Texas Health
Sciences Center at San Antonio, used a specially formulated,
time-release rapamycin supplement in their laboratory mouse chow.
Interestingly, the mice were not exposed to rapamycin in the diet until
they were middle-aged, or, as the study reported, "roughly the
equivalent of a 60-year-old person." Even so, the drug had a profound
effect on lifespan.
Rapamycin was originally discovered in soil samples
on Easter Island (Rapa Nui), famous for its towering, long-faced, stone
Moai statues. Rapamycin already has a clinical role in reducing
rejection of transplanted organs, in treating advanced kidney cancer,
and in preventing narrowing of the heart's arteries after corrective
surgery.
The study of rapamycin's longevity effects was part
of the National Institute on Aging Interventions Testing Program. It
accepts nominations for compounds from members of the scientific
community, and selects the most promising to undergo parallel testing at
three different institutions. Several compounds have been tested, but
rapamycin is the first to significantly increase lifespan at all three
centers in both male and female mice.
Rapamycin, which Kaeberlein, Kennedy and Dr.
Stanley Fields, professor of genome sciences, had previously shown
increases life span in yeast, is know to inhibit an enzyme called TOR.
TOR activity is regulated by nutrient availability.
Prior work by these
UW scientists indicated that reducing TOR activity is central to how
dietary restriction slows aging in yeast. Dietary restriction has long
been known to slow aging in mice and to protect animals against
age-related disorders like cancer, obesity, and heart disease. In the
commentary, the authors suggest that the possibility that rapamycin is
mimicking the effects of dietary restriction in mice merits further
study.
The commentators also warn that healthy people
shouldn't take rapamycin to slow aging because it can suppress the
immune system. However, they don't rule out the possibility that
rapamycin -- or more sophisticated interventions to reduce TOR activity
-- might someday prove useful against age-related diseases. They also
speculate that drug strategies might be discovered in the relatively
near future to provide similar disease-fighting and longevity benefits
without unwanted side effects.
The authors concluded: "Although extending human
lifespan with a pill remains the purview of science fiction for now, the
results of the study by Harrison and his colleagues provide reason for
optimism that, even during middle age, there's still time to change the
road you're on."
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