UF Studies Find Key To Preventing Strength And Muscle Loss In Elderly

November 24, 2003

GAINESVILLE, Fla. — Hair dye and wrinkle cream can erase some of the outward signs of aging. Now University of Florida researchers may have discovered a way to turn back the clock on the physically devastating loss of strength and muscle mass.

In tests on rats, UF researchers found lifelong calorie restriction not only significantly reduced the death of muscle fibers and the resulting loss of muscle tissue, it also halted the decline in strength that naturally occurs with aging.

In fact, calorie restriction worked so well the rodents experienced almost no muscle loss after middle age, the point at which those fibers typically stop growing. More surprising, their muscles remained as strong in old age as they had been in early- to mid-life, when they typically reach their peak, the researchers said.

At a time when people are living longer, the findings hold tremendous possibilities for preventing falls and hip fractures, major causes of disability and death in the elderly, said Christiaan Leeuwenburgh, director of the Biochemistry of Aging Laboratory at UF’s College of Health and Human Performance.

“As we age, the key issue is very simple: We become weaker. Now we’ve found in these studies that we can prevent the loss in (muscle) function, and we can prevent cell death,” Leeuwenburgh said.

“That’s exciting, very exciting, because a lot of people, even my grandfather, fell at an old age and that was because he had weak muscles, and he died very shortly after,” said Leeuwenburgh, who also is affiliated with UF’s College of Medicine. The results of his two studies, funded by the National Institutes of Health, will be published in the December issue of the Journal of Applied Physiology and the January issue of Free Radical Biology and Medicine.

Each year, more than one-third of Americans over 65 sustain falls, the leading cause of injuries and injury-related deaths. The total cost of fall injuries for people 65 and older was $20.2 billion in 1994, and that is expected to reach $32.4 billion by 2020, according to the Centers for Disease Control and Prevention.

Muscle cell damage in people begins about age 40 and eventually leads to the destruction of progressively larger areas of muscle and accompanying weakness. People can lose as much as half of their type 2 muscle fibers – the so-called fast-twitch type that control quick movements – over their lives, Leeuwenburgh said.

He and colleague Amie Dirks found this damage is caused by apoptosis, a genetically programmed series of events leading to cell death. Apoptosis can occur as a normal process to destroy old cells in order to make new ones, or as a result of disease or illness.

While this programmed cell death has been found in other types of muscle, the UF study is the first to discover evidence of it in skeletal muscle fibers, which contain numerous nuclei, many of which must die in order to kill the fiber, Leeuwenburgh said. Just how many remains unknown, he said.

Muscles house mitochondria, the energy-producing structures of cells that also control apoptosis. When mitochondria are damaged, they can release free radicals, which are proteins that cause cells to die. The researchers found significantly elevated levels of these destructive proteins in the fast-twitch muscle fibers in a rear leg muscle of 11 26-month-old rats – the equivalent of about 70 to 80 years in people – that were allowed to eat as much as they wanted.

In another group of nine old rats whose calorie intake was restricted over their lifetimes by 40 percent relative to their counterparts’, however, the levels of these proteins remained the same as those of the young 12-month-old rats — the equivalent of 30 to 40 years in people, he said.

Leeuwenburgh and co-researchers Anthony Payne and Stephen Dodd also found that muscle strength – measured by passing an electric current through muscles to cause contraction and mapping the resulting force by computer – declined with age by 27 percent in a fast-twitch front leg muscle of 10 rats that ate as much as they wanted.

Among 10 that had been calorie restricted over their lives, however, strength remained the same, not only when researchers looked at the ratio between strength and body mass but when they analyzed the amount of muscle with respect to body mass, he said. No significant differences were found in a rear leg muscle of mice that contained mostly slow-twitch fibers.

In addition, while the space between muscle fibers – called extracellular space – typically increases as normal rats and people age, the researchers did not find this in the calorie-restricted mice. That might also help explain some of the functional declines in muscle that occur over time, Leeuwenburgh said.

“Muscle cells shrink a little bit (with age) and there’s more garbage between them,” he said, an accumulation of ”advanced glycoxidation end products that are not healthy, they’re not helpful, they’re not good for anything.”

The idea of cutting calories to boost strength might seem radical to some, said Leeuwenburgh, who restricts his own calorie intake. But he said that while their total calories were cut by 40 percent, the calorie-restricted rats received the required amounts of protein, vitamins, minerals and other nutrients. In people, 40 percent would amount to cutting out, on average, a loaded fast-food hamburger and fries a day.

“We all know that if we want to get stronger, we need to perform resistance exercises, and we definitely need to eat proteins,” Leeuwenburgh said. “These animals are not malnourished- they simply get less food.”

Leeuwenburgh “has some interesting results” providing evidence that calorie restriction can ease some of the effects aging has on the body, but much work remains to be done, said Huber Warner, associate director of the National Institute on Aging’s Biology of Aging Program. “The issue is to figure out how calorie restriction works so we can find a way to mimic that, but still delay the adverse changes that occur with aging, without actually greatly reducing our caloric intake.”