Frailty not an inevitable symptom of aging Scientists predict treatments will break 'vicious cycle'

Throw out another convention of old age. Researchers are finding that frailty may not be the inevitable result of aging but rather is a preventable and perhaps treatable condition.

The muscle weakness, exhaustion, and weight loss typical of frailty were until recently considered just byproducts of diseases and the general loss of vitality during one's advanced years. Now scientists are studying the condition in its own right.

The focus on frailty reflects the aging population as well as medicine's increasing interest in improving the quality of life of seniors, not just prolonging their lives. Over the last few years, the National Institutes of Health has funded dozens of studies to define the condition and search for causes. Major academic conferences in 2004 and 2005 and pivotal research papers in the last few months provided evidence that frailty is a constellation of symptoms that may have a common cause, and that frailty is not just a one-way street to decline.

"I suspect that within a decade, there will be some treatments," said Dr. Thomas Gill, a professor of medicine at Yale University.

Already, there is preliminary evidence that exercise can ward off or reduce frailty, and pharmaceutical companies are developing drugs to target particular symptoms, such as muscle weakness. Recent studies have linked frailty to low levels of hormones, as well as to malnutrition, anemia, and chronic inflammation, providing fertile ground for treatments. The ultimate goal is to prevent the decline of millions of Americans into a weakened condition that often leads to disability, hospitalization and death.

A number of leading researchers in the field, including Dr. Lewis Lipsitz, vice president for academic medicine at Hebrew SeniorLife, believe the underlying causes of frailty are a breakdown in many of the biological systems that keep humans healthy -- those that protect us from disease, that control the makeup of blood, and that maintain muscle strength.

The result is often a loss of physical resiliency. "Frailty is where any new thing that comes along is going to topple you over," Lipsitz said.

Dr. Linda Fried, director of the Center on Aging and Health at Johns Hopkins University, suggests that frailty develops as a result of a vicious cycle in which disease, medications and environmental factors combine to cause malnutrition, which leads to muscle weakness. That in turn causes a decrease in activity and less incentive to eat well. The weakness can lead to impaired balance, falls, and injury, as well as other diseases.

Fried has developed a definition of frailty that is quickly becoming the standard. Under this definition, individuals with three or more of the following symptoms are considered frail: weight loss, decreased daily activity, muscle weakness, exhaustion, and slow walking speed. Those with two symptoms may be considered at risk of frailty.

Researchers estimate that at least 7 percent of those over 65 are frail, and about 20 percent of those over 80.

Two years ago, Esther Perlman-Kane, then 84, was weak and tired and found it difficult to walk. Part of the problem was an aching injury to her back, leg and groin, but it was more than that. Sometimes just getting through the day was difficult. She felt vulnerable and rundown.

"I'd be afraid to be with people who had colds," she said.

Then she moved into a seniors apartment complex in Randolph that has a gym and a fitness instructor and decided to start a fitness program.

Perlman-Kane gets a twice-weekly aerobic workout on a recumbent step machine and strengthens her muscles on weight machines. She's up to 166 pounds on the leg press and 56 pounds on the triceps pull. After a year of exercise, she no longer sees herself as frail. She walks spryly through the hallways and energetically leads art classes for other residents, drawing on her long career as a portrait artist.

There is growing evidence that physical exercise similar to Perlman-Kane's workout can prevent or reverse frailty. "That would be wonderful," she says. "Nobody wants to be frail."

Studies have shown that weight training strengthens muscles, even in very old individuals, while also reducing inflammation and helping to prevent falls. Researchers are about to launch a definitive study to determine if a combination of aerobic exercise, weight lifting and balance training can help frail sedentary individuals retain the ability to walk at least four blocks. Led by Dr. Marco Pahor, director of the University of Florida Institute on Aging, the study is expected to track 2,500 older men and women for four years.

Work on drugs that might treat or prevent symptoms of frailty is under way, but so far nothing has been proven to help patients.

One focus is testosterone, which decreases with age in men. Some studies suggest that giving testosterone to men with low levels of the hormone could strengthen muscle, increase bone mass, and improve quality of life, but the extra testosterone might also cause harmful side effects such as blood clots.

Now, the National Institute on Aging is funding several large studies to provide more definitive evidence on testosterone's effects and to track side effects.

Several major drug companies are testing medicines designed to stimulate growth hormones to see if they can promote increases in muscle mass and strength. Wyeth, in its Cambridge research facility, is trying a different tack -- a drug designed to block muscle wasting. These drugs have shown enough promise to move into the second of three phases of testing required by the Food and Drug Administration to ensure safety and efficacy.

Yet another avenue that scientists say may prove fruitful is ACE inhibitors, the drugs that many seniors already take to control blood pressure. Two studies of patients taking the drugs for their hearts found they were stronger and more vigorous than those taking other blood pressure medications.

The ACE inhibitors have yet to be tested directly for muscle strengthening.

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