Miracle Muscles : UCI Researchers Seek a Pill to Manipulate Growth and Stimulate Brawn Without Exercise

Pump iron for a month and, presto, your muscles get stronger.

Take to your La-Z-Boy for a month and your muscles go soft.

Everyone knows this happens, but no one knows exactly why. Why should you have to work to keep your muscles in shape? Why can’t you relax and take a pill that duplicates two hours at the gym?

The surprising answer is: One may be on the way. Depending on which scientist you ask, it’s just around the corner or it’s 40 years away. But researchers agree they are closing in on the most basic, biological processes by which muscles decide whether to become stronger or weaker, quicker or slower.

Researchers are already beginning to manipulate the process. One chemical administered to laboratory rats duplicates some effects of daily workouts.

Does this mean that someday couch potatoes can look like Arnold Schwarzenegger? Probably not, says Kenneth M. Baldwin, professor of physiology and biophysics at UC Irvine and a leading researcher in the field.

But it does mean that the muscles of people with cancer and AIDS may not become so debilitated. And it might mean that ordinary people, who typically become sedentary and start weakening around age 60, can enjoy a stronger, less accident-prone old age.

But first in line to benefit are the people who have paid for so much of the research: the National Aeronautics and Space Administration.

Since the early days of space flight, they and their Russian colleagues have been trying to prevent the weakened muscles caused by the zero gravity of space. Early Soviet cosmonauts, the first to be aloft for long periods, sometimes could not even stand up after returning to Earth.

Trial-and-error experiments with muscle-taxing space suits and exercise equipment have yielded only slight gains. Baldwin--who has a 10-year NASA research grant and serves on three NASA science advisory committees--and other researchers have taken a different approach. They are studying how muscles work at their most basic level in hopes of isolating the process that keeps human muscles strong so they can duplicate it with safe drugs.

They say they are closing in.

They have discovered that muscles react not only to the amount of stress placed on them but to the type of stress, rapid or slow. Somehow these distinctions are transmitted to the genes in muscle cells, which then produce the appropriate kinds of muscle fibers.

The muscles become not only stronger or weaker but can change their very character. They may switch, say, from muscles with stamina and efficiency to muscles that provide short bursts of power and speed. Muscle research today is concentrating on just what signals make these changes take place, and, to find the answers, researchers are looking down to the level of the muscles’ molecules.

You know what your muscles look like if you have ever examined a beefsteak. They are not a solid mass but a dense package of thin, fleshy layers.

View one of these layers through a very high-powered microscope and you can see the actual engines of the muscle--the millions upon millions of muscle filaments. Each is composed of short chains of protein molecules called myosin and actin, which together provide all of the muscle’s movement and force.

The actin chain lies atop the myosin chain like a sliding hatch. When the muscle fiber is relaxed, the hatch lies “open,” and the two chains are at their greatest combined length. But when the myosin receives the power command, it pulls the hatch “closed.” That shortens the combined length of the two chains and provides the filament’s tiny share of the muscle’s contraction.

This filament’s force is all or nothing, Baldwin says. It always applies the same amount at the same speed. Equivalent types of filaments are identical in Michael Jordan and Mother Theresa. But there the resemblance ends.

The filaments are bundled into muscle fibers about the size and shape of a thin hair a few millimeters to a few centimeters long. Jordan’s fibers are perhaps twice as thick as Mother Theresa’s, because physical conditioning and the male hormone testosterone have added more filaments for additional strength.

About 100 to 500 fibers are wrapped together like a package of spaghetti to form a “motor unit,” the smallest muscle unit that can be controlled individually. When Jordan shoots a basketball, his brain calculates just how many and which motor units are required in various muscles and activates only them. If the calculation is correct, Jordan scores.

Your genes may not have endowed you with a professional athlete’s muscle makeup, but you make similar calculations every time you lift a box or open a door.

The brain’s orders reach the muscles because a nerve from each motor unit is plugged into the spinal cord like a telephone plugged into a wall socket. But unlike the telephone, if you unplug the muscle, it still works.

The reason is that muscles take orders from more than the brain, Baldwin says. Some nerves from motor units go to the spinal cord and up to the brain, but others loop back and connect to other motor units, to the skin and to other body tissues.

Through these loop-back circuits, muscles and skin can communicate among themselves, allowing muscles to react faster than the brain can. The classic example is touching a hot surface. Your skin sounds the alarm, and the muscles pull your hand away before the news even reaches your brain.

Similar, routine reactions are happening in your body every waking instant. The fact that you can, without thinking, stand on two legs or hold your head erect is due to direct communication among muscles assigned to oppose gravity.

In fact, some tasks are easier to do if you keep your brain out of it. Cocktail servers are taught to balance their drinks on a tray supported by the palm of one hand and to avoid watching it. Even the most top-heavy trays rarely spill, because the arm and hand muscles balance the tray continually and automatically. But start watching the tray and the brain will almost always over-correct and spill.

Such muscle communication can be incredibly sophisticated. Cats that have lost all nerve communication between brain and legs can still walk on a treadmill with only the slightest loss of coordination, Baldwin says.

This back-door communication is the key to why our muscles change, Baldwin says. Through this system, signals flow to muscles and prompt quick adaptations.

Muscles can change because they are constantly being built and rebuilt, Baldwin says. In only seven to 14 days, half of the protein in your muscle cells has been broken down, discarded and replaced.

“It’s as if you had a contractor constantly tearing down the rooms in your house and rebuilding them with new materials,” Baldwin says. “After a month, you’ve got a brand new house. Next month you’ll have another brand new one.”

What every body builder knows is that increased stress on muscles--lifting more weight than you did last week--somehow signals cells to build bigger, and therefore stronger, muscles. (Bigger muscles are always stronger, Baldwin says.)

But what more recent studies discovered is that a further change takes place. The character of the stress was changing the character of the muscle fibers.

Marathon runners were developing a type of slow-moving but high-stamina fiber, which was named Type I or “slow twitch.” Sprinters and power lifters were developing a type of high-speed, high-output fiber--a group called Type II or “fast twitch.”

The typical person has half one type, half the other throughout the body. But when muscle cells are somehow informed of the type of unusual activity the muscle is performing--slow-moving or fast, long-lasting or intense--some muscle fibers change character to the appropriate type, Baldwin says.

The change begins quickly, according to Baldwin’s research associate, Vince Caiozzo, assistant professor of orthopedics at UCI’s College of Medicine.

“We have rats that pump iron. It sounds funny, but they aren’t standing up curling weights. They take their feet and push against an object. The whole thing is computerized, so it can simulate every aspect of you going to the gym.

“If we have them do about two minutes of weight training a day, within two days we begin to see changes in the (muscle fiber types) they are producing.”

Five of Baldwin’s rats went up on a space shuttle in November to determine just what was happening to muscles in space. On their return, Baldwin discovered that being in zero gravity for 14 days had converted a large portion of their muscle fibers from Type I, which is particularly suited to opposing gravity, to Type II.

Muscles, freed from the effects of gravity, were merely adapting to their new environment, normally a good thing. “When they’re up in space, they no longer need their legs to balance and control gravity,” Baldwin says. “They can float around from one location to another with just fingertip force.”

But astronauts return to Earth suddenly, where zero-gravity adaptation instantly becomes a liability. They found that not only were the muscles that helped them stand weakened, the nervous system that operated their muscles had become lazy in weightlessness. So had the astronauts’ breathing and blood circulation systems. In some cases, the astronauts could not stand without fainting.

This is merely an inconvenience when returning to Earth. With the flight over, the astronauts can spend several days or even weeks to work back to normal.

But it could be a major problem on a long mission to another planet.

“Let’s take Mars; that’s where they plan to go next,” Caiozzo said. “It’s projected to take 1 1/2 years just to get there. The problem is, when they land on Mars (and once again encounter gravity), are they going to be able to function?”

So far, Baldwin says, exercise programs in space using treadmills, cycles and bungee cords have not solved the problem. The solution, he says, is more likely to be a combination of physical stress and drugs that either prevent the change in muscle fibers or deceive the muscle cells into thinking they’ve been exercising.

Tests on Baldwin’s rats have shown that a chemical called beta guanidinopropionic acid acts to deplete muscles of a naturally occurring substance called phosphocreatin. Normally, this substance is used up when muscles work. Baldwin believes that artificially depleting it makes cells react as if the muscles had been through a workout. So far, rats have reacted to the chemical by converting some Type II muscle fibers to Type I fibers.

Removing the thyroid hormone from circulation seems to block the conversion of muscle fiber that occurs in zero gravity, Baldwin says. This shows the process can be regulated chemically, he says.

Changing or maintaining muscle size is a different matter, Baldwin says. Researchers believe that the simple brute force generated by muscles serves to signal how much muscle mass is needed. The muscle builds up or shrinks accordingly.

“We have not been able to unlock a chemical that would act in place of force, but we think we have some clues,” Baldwin says. A substance now available called insulin-like growth factor is being studied. It seems to work directly on muscle cells to increase their size, Baldwin says. Unlike steroids, the increase in size occurs without exercise.

(It appears that steroids only allow a person to exercise more strenuously; it is the increase in exercise that actually increases muscle size, Baldwin says. Steroids administered to a couch potato would probably have no muscle-building effect, but this has not been scientifically tested.)

Another researcher in the field, Frank Booth, professor of physiology at the University of Texas Medical School in Houston, believes the answer may be genes rather than drugs. Injecting certain genes into muscles like a vaccination could promote production of desired substances within the muscle that would maintain muscle fiber without exercise, he says. Something that could be used by human beings is only five to 10 years away, he estimates.

“What I’m describing will be possible on a very limited scale for a very few people,” Booth says. “I don’t think it would be used by the normal population. It would probably be used very selectively. I think it would be costly and not applicable in all cases.”

But, he adds, subsequent advances “may take it to the general public.”

V. Reggie Edgerton, professor of physiological science at UCLA and another researcher in the field, says he is concentrating on the nervous system. It is already known that the efficiency of a body’s nervous system plays a role in how much force its muscles can apply.

Within certain bounds, a person with smaller muscles but a better nervous system can be effectively stronger than the person with the opposite attributes. Edgerton and others say the typical person cannot voluntarily exert all the potential force of his or her muscles. But some scientists disagree, and the point remains controversial.

Edgerton says the nervous system may by itself play a role in determining how muscles will change, but “we’re pretty far away from knowing all the answers.

“Humans have been wanting to believe there’s an easy way for a long time. Do you remember that book about how to stay fit with only 30 minutes of exercise a week? It stayed on the bestseller list for months. It just told everybody what they wanted to believe.”

Only 10 years ago, muscle biologists thought every property of muscles was determined by the muscle’s activity. Now it’s now plain that’s not true, Edgerton says.

“I think we could easily get to the point where we could minimize some of the negative effects of aging” by controlling the chemistry of muscle cells.

Movement Mechanics

Muscles consist of bundles of fibers connected to the brain by nerves. The nerves carry chemical messages telling the muscles when to contract and how much exertion is needed. Almost all muscles move the bone connected to the joint just below the muscles affected. A look at the muscle system when the lower arm is raised:

Origin: Where muscle attaches to bone that does not move with each contraction of the biceps.

Muscle pairs: Biceps and triceps work together. As one contracts, the other relaxes.

Triceps: As it contracts, elbow straightens.

Biceps: As it contracts, elbow bends.

Insertion: Where muscle attaches to bone that moves with the bicep’s contractions.

Elbow joint

Forearm: Muscles flex and extend the hand and fingers.

* The Inside Story

Filaments are the muscle’s engines. Each filament is composed of chains of proteins, myosin and actin.

Muscle fiber

Filament

Myosin

Actin

To provide movement, myosin pulls actin toward it. When resting, the myosin-actin interaction is inhibited and tension is relaxed. * Pulling the Weight

Humans have 700 muscles comprising about 50% of body weight.

Eye: Fastest contracting muscles in the body.

Ear: Smallest muscle; steadies bone in middle ear.

Tongue: Almost all muscle; fibers provide complex movement.

Face: It takes 14 muscles to smile.

Heart: Muscle with greatest endurance; beats about 100,000 times a day.

Back: Moves spinal column; strained back is second highest cause of lost work days.

Buttocks: Largest combined muscle group in body.

Thigh: Potentially strongest--yet least used--muscle in the body.

Foot: Humans lost grip and precision manipulation muscles when they became bipedal. Sources: UC Irvine, Dr. William Honigman, World Book Encyclopedia, American Medical Assn. Encyclopedia of Medicine.

Researched by APRIL JACKSON / Los Angeles Times