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Why Do Workouts Work?

By exploring how and why exercise causes muscles to grow, scientists hope to help astronauts avoid muscle atrophy.

by Patrick L. Barry

Most machines don't improve with use. Old pickup trucks don't gradually become Ferraris just by driving them fast, and a pocket calculator won't change into a supercomputer by crunching lots of numbers .

The human body is different. As weightlifters know, the more that people use their muscles, the stronger they become. And unused muscles do not remain preserved; neglect causes them to waste away, or atrophy.

It's a remarkable response, one that scientists don't fully understand. Somehow, muscle cells "sense" how they're being used and then remodel themselves to better fit the task. How does this happen? And what exactly is it about exercise that triggers the changes?

NASA needs to know the answers. Astronauts in space exercise furiously to keep fit. Even so, their muscles tend to weaken.

"Normally, people's muscles do a lot of work that they're hardly aware of - lifting their bodies and maintaining posture against gravity. In space, that constant muscular work is removed. There's a danger of atrophy," explains Kenneth Baldwin, a professor in the Department of Physiology and Biophysics at the University of California, Irvine.

Heavy use doesn't wear muscles out; instead they grow bigger and stronger.

With NASA support, Baldwin is researching the inner workings of muscles and plumbing the fundamental mystery: Why do workouts work?

NASA has a special interest in isometric exercises - i.e., non-moving exercises where an astronaut pushes hard against a fixed surface. Motionless exercises allow for simple lightweight equipment less expensive to launch and less prone to break during a mission. But are they effective?

To find out, Baldwin's group gave laboratory rats a workout by activating the rodents' leg muscles with painless electrical stimulation. They tested three types of exercise: muscle contraction, muscle lengthening, and isometric, where the muscle exerts a force while remaining the same length. (Just think of doing push-ups: muscle contraction occurs in the "up" part of a push-up, muscle lengthening during the "down" part, and isometric while holding a push-up midway.)

After the sessions, the scientists performed tests to see how the rats' muscles responded. "What we found," says Baldwin, "was that after 12 sessions, all three types of workout tended to provide about the same amount of muscle growth," even the isometric exercises that involved no motion.

This was nothing new. Other scientists had come to the same conclusions before. But Baldwin's group took their analysis a step further:

Each muscle cell contains many small bundles of contractile proteins, called myofibrils. These contractile proteins do the work of muscle contraction.

In addition to measuring overall muscle mass - how "buff" were the rats? - they also measured the amount of contractile proteins within the muscle cells. Contractile proteins are what actually cause a muscle to contract. They are what give a muscle its strength.

To their surprise, Baldwin's team found that while isometric exercises did prevent leg muscles from withering, they did not stop a decline in the amount of contractile proteins in those muscles. The muscle was actually degrading on the molecular level.

No one knows why this is so, but one thing seems clear: Isometric exercise might not be the best way to maintain astronaut muscles. Baldwin plans to investigate further with just-renewed funding from NASA.

A more unconventional possibility is that astronauts could stave off muscle atrophy by taking a pill. Anti-atrophy pills are only speculative right now, Baldwin says, but there are reasons to believe that they might be possible. That's because when atrophy sets in, the muscle isn't just withering away passively - it's actively breaking itself down!

A complex network of enzymes within the muscle's cells disassembles muscle proteins molecule by molecule. "In order to chop those proteins up, you use a lot of energy," notes Baldwin. If scientists could pinpoint a key "lynchpin" enzyme in this network, they may be able to design a drug to block its action, thus slowing the breakdown of the muscle.

Astronaut Peggy Whitson works out onboard the International Space Station

This active breakdown of muscle protein is going on all the time in everybody's muscles, as is the constant assembly of new proteins. Whether a muscle grows, shrinks, or stays the same size depends on the balance between these rates of destruction and construction, a bit like the water level in a bathtub that's both filling and draining at the same time.

Baldwin is taking a look at the mechanisms behind the "construction" half of this balance. In particular, his group is focusing on a hormone called Insulin-like Growth Factor 1 (IGF-1). Muscles produce IGF-1 in response to strenuous exercise, and this hormone in turn activates enzymes in the muscle cells that cause the cells to grow. Indeed, Baldwin found that levels of IGF-1 in the rats' muscles were higher just after exercising.

"Some people think that it's the mechanical stress that turns the gene (for IGF-1) on, but we really don't understand that process yet. What we do know is that IGF-1 triggers muscle growth," Baldwin explains.

Might supplements of IGF-1 be used to ensure that construction of muscle proteins keeps pace with protein destruction in astronauts? Baldwin says they're entertaining the idea and are already discussing ways in which that might be done.

If they're successful, it will be good news for more than just astronauts. After all, we're all owners of that incredible, self-adapting machine called the human body.

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First Science 2014