[extropy-chat] antiepilepsy drugs lengthen worm lifespan

[Eugen Leitl]

http://www.sciencemag.org/cgi/content/full/sci;307/5707/193a

BIOMEDICINE:
As the Worm Ages: Epilepsy Drugs Lengthen Nematode Life Span
Ingrid Wickelgren

Although pharmacists have proven medications for ailments as varied as
migraines and bacterial infections, they have little to offer in the fight
against aging other than unproven remedies. But new evidence suggests that
the right prescription for longevity may already be hidden behind the
pharmacy counter.

Geneticist Kerry Kornfeld and his colleagues at Washington University in St.
Louis, Missouri, report on page 258 of this issue that a class of antiseizure
drugs markedly extends the life span of the roundworm Caenorhabditis elegans.
The scientists screened 19 classes of medications prescribed for other uses
for potential longevity effects. "These compounds are approved for human use,
so they have [molecular] targets in humans," says Kornfeld, although he
cautions that there is no evidence yet that the anticonvulsants he tested
slow aging in people.

Because these drugs act on the neuromuscular systems of both humans and
worms, the finding also hints at a direct link between the neuromuscular
system and the aging process, says geneticist Catherine Wolkow of the
National Institute on Aging in Baltimore, Maryland. Furthermore, the data
indicate that although the drugs' mechanisms of action partly involve
molecular pathways already known to govern aging, those pathways tell less
than the whole story. "The work opens up the possibility that there may be
new targets not yet explored that affect aging and neuromuscular function,"
says Wolkow. "That's a pretty important finding."

With a life span of a few weeks in the lab, C. elegans is a favorite subject
for longevity studies. Since the early 1990s, researchers have linked
mutations in dozens of worm genes to extensions of the creature's lives.
Given all the drugs on the market, Kornfeld speculated that at least one of
them was likely to retard aging or promote longevity by affecting those gene
targets.

    Figure 1 Staying alive. Anticonvulsant drugs promote longevity in
roundworms like this one.

    CREDIT: THE NATIONAL HUMAN GENOME RESEARCH INSTITUTE

So about 4 years ago, Kornfeld's graduate student Kimberley Evason began
exposing separate groups of 50 worms to various drugs, from diuretics to
steroids, at three different dosages. Most of the compounds the worms ate off
their petri dishes had toxic effects. After 8 months of negative results,
Evason tested the anticonvulsant ethosuximide (Zarontin). A moderate dose,
she found, extended the worm's median life span from 16.7 days to 19.6 days,
a 17% increase. Lower doses had a lesser effect, and higher doses were toxic.

Evason then discovered that two related anticonvulsants also lengthened
worms' lives, one of them by as much as 47%. By contrast, a chemically
related compound that does not have antiseizure activity had no similar
effect. That is "nice evidence" that the compounds' ability to extend life
span is related to their effectiveness as anticonvulsants, says geneticist
Javier Apfeld of Elixir Pharmaceuticals in Cambridge, Massachusetts.

The drugs are thought to control seizures in people by acting on certain
neuronal calcium channels. Exactly how the drugs extend life span in worms is
unknown, although they seem to stimulate the nematode neuromuscular system.
Kornfeld's team discovered that the drugs affect two types of neurons: those
that govern egg laying, leading to earlier release of eggs, and those that
control body movement, making the worms hyperactive.

Unlike many of the genetic mutations that affect worm longevity, the drugs
don't act primarily through the worm's insulin-like signaling system, the St.
Louis group revealed. For example, treatment with two of the anticonvulsants
still lengthened the lives of worms with life-curbing mutations in an
insulin-pathway gene. "We think the nervous system effects are more
complicated than simply regulating insulin signaling," Kornfeld says.

The next step is to test whether the drugs have any antiaging effects on
higher organisms, such as flies and mice. "The nervous system might have a
central function in coordinating the progress of an animal through its life
stages, leading ultimately to degeneration," Kornfeld speculates. Still, he
adds, "it's very early days for understanding the connection between neural
function and aging."

-- 
Eugen* Leitl <a href="http://leitl.org">leitl</a>
______________________________________________________________
ICBM: 48.07078, 11.61144            http://www.leitl.org
8B29F6BE: 099D 78BA 2FD3 B014 B08A  7779 75B0 2443 8B29 F6BE
http://moleculardevices.org         http://nanomachines.net
-------------- next part --------------
A non-text attachment was scrubbed...
Name: not available
Type: application/pgp-signature
Size: 198 bytes
Desc: not available
URL: <http://lists.extropy.org/pipermail/extropy-chat/attachments/20050119/911ef279/attachment.bin>