Science News - June 4, 2011

Rapamycin inhibits a series of reactions in a cell that begins with a protein called (in a practical bit of nomenclature) “target of rapamycin,” or TOR. The TOR chemical pathway is one of life’s fundamental processes; it exists in some form from yeast to mammals, where it is designated m TOR, and helps regulate cell growth, the production of ribosomes (cellular protein factories) and protein turnover. m TOR, in turn, activates a protein called S6K1.

In 2009, a team led by British researchers reported in Science that mice with mutations that left them without any functional S6K1 lived longer. Just as significant, genes in the mice were switched off and on in patterns consistent with calorie restriction. A study in Nature in 2009 reported that rapamycin could extend life span in mice, even when the drug was given during older age. Last year, writing in Cell Metabolism, European researchers reported that rapamycin also extends the life span of flies, while another report in the American Journal of Pathology described an extension of life span in cancer-prone mice.

“As far as rapamycin goes, it works,” says Luigi Fontana, a physician and calorie restriction researcher at Washington University in St. Louis. “By giving rapamycin, you are telling the cells that there is not enough energy.” But rapamycin has its drawbacks. Most notably, the drug is given to transplant patients because it suppresses the immune system. This hasn’t been an issue in mice because the animals are housed in pathogen-free environments. “Human beings are not living in pathogen-free facilities,” Fontana says. “I would never take rapamycin.”

The immune system concerns will probably keep the drug, at least in its current form, off the antiaging market. “It will not be prescribed to healthy people because it is labeled as an immuno-suppressant,” says Mikhail Blagosklonny, a scientist studying cell stress biology at the Roswell Park Cancer Institute in Buffalo, N. Y. “This is enough to make people scared.” Blagosklonny (who has helped form a company, Tartis-Aging, to develop

Life expectancy in years

80 and over 70–79 60–69 50–59 Under 50

SOURCES: GUINNESS WORLD RECORDS; WHO WORLD HEALTH STATISTICS; UN WORLD POPULATION PROSPECTS: THE 2006 REVISION Averages and outliers Jeanne Calment of France was 122 when she died in 1997, making her the longest-lived person known. That a small percentage of people live beyond 110 raises the possibility of extending average human life span and motivates scientists’ search for antiaging drugs. For 2009, global average life span was 68. But substantial differences exist: The map shows average life expectancies for people born between 2005 and 2010, broken down by country.

rapamycin as an antiaging drug) believes
that in the smaller doses that would be
given to healthy people, rapamycin
would not dampen the immune system.
Writing last year in Cell Cycle, he even
went so far as to say that “taken together
with its ability to suppress cellular aging
and to increase life span, this may call
to re-label rapamycin from immuno-
suppressant to aging-suppressant (gero-
suppressant).”
If that doesn’t happen, the body’s
biology offers plenty of other targets for
drugs. Acting on the body’s system of glu-
cose detection and insulin production,
the diabetes drug metformin has also
been an attractive antiaging candidate.
And in the future, scientists may be able
to capitalize on the signals from mito-
chondria (a cell’s energy factories) that
affect life span independently of calorie
restriction. In January, researchers from
the Salk Institute for Biological Sciences
and the Scripps Research Institute, both
in La Jolla, Calif., announced in Cell that
they had pinpointed a chemical distress
signal put out by mitochondria that
lengthened the life span of worms. In
the experiment, the signal was produced
only in the intestine and nerve cells, yet
affected the entire organism.

Should any new compound reach
commercial development, scientists
acknowledge that the resulting antiaging
drug would still face hurdles to reach the
aging public. A drug that might be taken
in otherwise healthy people, perhaps for
years, would need to demonstrate it was
safe beyond doubt.