Move over, steroids. Take a hike, human growth hormone.
If scientists are right, a simple pill can enhance and even mimic the
beneficial effects of exercise. At least in mice. But some people may
not be waiting for research to show that the compounds work in people as
well. The scientist who discovered the drugs, which are a cinch for
chemists to synthesize, believes they may already be in athletes’
equipment bags—since anti-doping agencies had no idea they should even
be on the lookout for them. The drugs, called AICAR and GW1516, work by genetically reprogramming
muscle fibers. The result is that the fibers use energy more
efficiently, allowing them to contract repeatedly without tiring. Mice
given the drugs ran faster and—this is where marathoners should prick up
their ears—44 percent longer on the treadmill than un-drugged mice
without flagging, Ronald Evans,
a Howard Hughes Medical Institute investigator at the Salk Institute
for Biological Studies in La Jolla, and colleagues are reporting today
in an advance online publication in the journal Cell.
The drugs also retool the muscles, with the result that there are more
slow-twitch fibers (the kind used for endurance exercises) and fewer
fast-twitch fibers (which let you put on bursts of speed, as in a
sprint). The drugs differ in just how much you—by which I mean a mouse, of
course—can get away with. GW1516 had a dramatic impact on endurance, but
to get the benefit the mice had to exercise. AICAR, on the other hand,
really does seem like the proverbial exercise in a pill: no exertion
required. The work builds on research that Evans reported in 2004, when he created genetically-engineered “marathon mice”
that had altered muscle composition and enough physical endurance to
run twice as far as normal mice. The genetic engineering basically
flipped a switch so that a gene called PPAR-delta was permanently “on.”
PPAR-delta is more prevalent in slow-twitch muscle fibers than in
fast-twitch ones, so keeping the gene turned on “increase[d] the amount
of non-fatiguing muscle fibers,” Evans said. The result was a mouse able
to run up to twice the distance of a normal littermate without
training. Despite whisperings that genetic engineering will be the next Olympic
doping scandal, it’s obviously easier to get the benefits of the
marathon mouse through a pill rather than gene splicing. But this
genetic switch was flipped when the animals were still embryos. That
raised the question, “what about reprogramming in an adult?” Evans said.
“When all the muscles are in place, can you give a drug that washes
over the muscle for a few hours at a time and reprograms existing muscle
fibers? That’s a very different question.” And it’s the question the new study answers with a resounding “yes.”
GW1516 acts in concert with exercise: Evans had two groups of mice run
on a treadmill for 30 minutes five days a week for a total of four
weeks. All of the mice, as expected, became more fit, able to run longer
and faster than when they were couch potatoes. But the animals that
also got GW1516 ran 68 percent longer than un-drugged mice. “The
dramatic effect of the drug was stunning,” Evans said. The second drug, AICAR, wowed them even more:
even in the absence of exercise, it activated many of the genes in
muscle that are turned on by exercise. After four weeks of swallowing
the drug, mice were able to run 44 percent longer than un-drugged
mice—despite never having set paw into the treadmill. “The mice were
behaving as if they’d exercised,” said Evans. Even better, actually:
mice on the drug ran longer and farther than mice that had dutifully
taken to the treadmill every day. Who said life was fair? Both drugs trigger a suite of changes that
underlie the improved endurance. They increase the number of
mitochondria (structures that produce energy) in muscle cells, and
increase blood flow. Evans suspects there were also beneficial changes
to the heart and lungs. That suggests that the drugs could give even
sedentary people the benefits of exercise. “Almost no one gets the
recommended 40 minutes to an hour per day of exercise,” Evans says. “If
there was a way to mimic exercise, it would make the quality of exercise
that they do much more efficient.” And for people who already walk, jog or run?
“If you like exercise, you like the idea of getting more bang for your
buck,” which GW1516 can provide, he says. “If you don’t like exercise,
you love the idea of getting the benefits from a pill,” as with AICAR. |