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Doctors seek to slow loss of muscle tone among aging

Doctors seek to slow loss of muscle tone among aging

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Bears emerge from months of hibernation with their muscles largely intact. Not so for people, who, if bedridden that long, would lose so much muscle they would have trouble standing.

Why muscles wither with age is captivating a growing number of scientists, drug and food companies, let alone aging baby boomers who, despite having spent years sweating in the gym, are confronting the body’s natural loss of muscle tone over time.

Comparisons between age groups underline the muscle disparity: An 80-year-old might have 30 percent less muscle mass than a 20-year-old. And strength declines even more than mass. Weight-lifting records for 60-year-old men are 30 percent lower than for 30-year-olds; for women the drop-off is 50 percent.

With interest high among the aging, the market potential for maintaining and rebuilding muscle mass seems boundless. Drug companies already are trying to develop drugs that can build muscles or forestall their weakening without the notoriety of anabolic steroids. Food giants like Nestle and Danone are exploring nutritional products with the same objective.

In addition, geriatric specialists, in particular, are trying to establish the age-related loss of muscles as a medical condition under the name sarcopenia, from the Greek for loss of flesh. Simply put, sarcopenia is to muscle what osteoporosis is to bone.

“In the future, sarcopenia will be known as much as osteoporosis is now,” said Dr. Bruno Vellas, president of the International Association of Gerontology and Geriatrics.

Researchers involved in the effort say doctors and patients need to be more aware that muscle deterioration is a major reason the elderly lose mobility and cannot live independently.

“A doctor sees old people who are shrinking and getting weak, but there is no medical terminology that’s been created and made uniform to allow the doctor to make a diagnosis, look at possible causes, and make a treatment plan,” said Dr. Stephanie A. Studenski, a professor of medicine at the University of Pittsburgh.

Of course, commercial interests are at play as well. “If you are trying to sell drugs, you want to have a very clear criterion for diagnosing the problem and for endpoints to treat it,” said Dr. Thomas Lang of the University of California, San Francisco, who is working on techniques for diagnosing sarcopenia.

A task force of academic and industry scientists met in Rome last November and in Albuquerque, N.M., last month and has submitted a proposed definition of sarcopenia for publication in a medical journal. The meeting received financial support from several drug companies and food companies.

Underscoring the focus on sarcopenia, four European medical societies proposed a somewhat different definition, and Studenski is developing yet another.

Whatever the definition, experts say, sarcopenia affects about 10 percent of those older than 60, with higher rates as age advances. One study estimated that disability caused by sarcopenia accounted for $18.5 billion in direct medical costs in 2000, equivalent to 1.5 percent of the nation’s health care spending that year.

Causes of the loss of muscle mass or strength might include hormonal changes, sedentary lifestyles, oxidative damage, infiltration of fat into muscles, inflammation and resistance to insulin. Some problems stem from the brain and nervous system, which activate the muscles.

Experts say the best approach to restoring or maintaining muscle mass and strength is exercise, particularly resistance training.

The National Institute on Aging is now sponsoring a controlled trial to test whether exercise can prevent disability in largely sedentary people, age 70 to 89. There is also some early evidence that nutrition, like vitamin D or high levels of protein, might help. “At this point, what we can say is that older people are at risk for eating too little protein for adequate muscle preservation,” said Dr. Elena Volpi of the University of Texas Medical Branch in Galveston.

Pharmaceutical companies are paying more attention to muscles, a part of the body they once largely ignored. A year ago, for instance, GlaxoSmithKline hired William Evans, a leading academic expert on sarcopenia, to run a new muscle research unit.

But with sarcopenia still not established as a treatable condition, “there is no real defined regulatory path as to how one would get approved in this area,” said R. Alan Ezekowitz, a research executive at Merck.

So for now, many companies are focusing on better defined illnesses like muscular dystrophy and cachexia, the rapid muscle wasting that can accompany cancer or other diseases.

One problem is that academic researchers and drug companies initially viewed sarcopenia as primarily a loss of muscle mass, a direct analogy to bone density in osteoporosis. Muscle mass can be measured by the same scans used for bone density.

But some studies have shown that strength, such as gripping force, or muscle function, as measured, say, by walking speed, is more important than mass in predicting problems seniors might have.

“There’s a lot more to the story than simply having a lot of muscle tissue,” said Brian C. Clark, an expert at Ohio University. “Most of the drug stuff has been targeting muscle mass.”

So the definition is shifting to include muscle strength and function. The academic-industry task force recommends testing whether a person can walk four meters, or about 13 feet, in four seconds.

That can be tested by any doctor, without the special equipment needed to measure muscle mass or strength, said Roger A. Fielding of Tufts University, a leader of the task force.

Experts say that to win approval from regulators and reimbursement from insurers, a drug must do more than merely improve mass or strength. It must, for example, improve walking ability or prevent people from falling.

Or perhaps it could restore mobility faster after a person is bedridden. Older people can lose so much muscle during a prolonged hospital stay that they have to move to a nursing home.

Demonstrating such benefits and cost savings would help counter criticism that doctors and drug companies are trying to turn a natural consequence of aging into a disease.

“If you can get out of a nursing home in three weeks instead of three months, wouldn’t we say it is a useful thing?” said Studenski, who consults for drug companies.

Efforts to develop muscle drugs are still in early stages, and there have been setbacks.

But for inspiration, researchers can look to the bears, though scientists have no definitive answer to the animals’ youthful secret.

Moreover, a study that has tracked 3,000 people for 50 years found that about 20 of them, now in their 80s, have not lost muscle mass.

“Maintaining the muscle is possible,” said Dr. Luigi Ferrucci of the National Institute on Aging, who directs the study, called the Baltimore Longitudinal Study of Aging. “We just don’t know the right formula yet.”


The hunt is on for alternatives to anabolic steroids, which build muscle by mimicking the effects of the hormone testosterone, but whose reputation has been tarnished by athletic doping scandals and side effects like liver damage.

A federally financed study showed that testosterone increased strength in the elderly. But the study was ended abruptly last year because those getting the hormone suffered far more cardiac problems than those getting a placebo.

Human growth hormone is also controversial because of side effects and questions about whether it can increase strength.

Companies like GTx and Ligand Pharmaceuticals are trying to develop drugs that possess the muscle-building ability of testosterone without its side effects, like the development of facial hair and other masculine features in women. These drugs are called selective androgen receptor modulators, or Sarms.

Pfizer, Amgen and Acceleron Pharma are separately pursuing drugs that block myostatin, a protein made by the body that acts as a brake on muscle formation.

Belgian Blue cattle, which do not make myostatin, have huge, rippling muscles and yet are otherwise apparently healthy. Several years ago, scientists reported that a German boy who lacked myostatin because of genetic mutations had abnormal strength and muscle mass.

Cytokinetics is testing a drug for Lou Gehrig’s disease that improves the ability of muscles to contract by, in effect, making them more sensitive to nerve signals.

Most of the drugs have been tested in only early-stage clinical trials so far, and there have been many setbacks.

Wyeth, now part of Pfizer, dropped a myostatin inhibitor that did not work well in a muscular dystrophy clinical trial. Amgen last month called off a trial to test its myostatin blocker for age-related muscle decline. Merck withdrew from a partnership to develop GTx’s drug.

But those companies all say they are not giving up on the quest.

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