A Molecular Explanation of Why Muscles Weaken With Age

Researchers can now tell you why your legs get creakier and wearier as you get older -- it's the inevitable deterioration of the genetic material in the energy-producing centers of your muscle cells.

"What we've shown here is an important first step to understanding aging in a specific organ of the human body," said Dr. Sreekumaran Nair, an endocrinologist at the Mayo Clinic and lead author of a report on the finding in this week's issue of the Proceedings of the National Academy of Sciences .

Nair and his colleagues took muscle samples from 148 healthy men and women aged 18 to 87 and looked at the DNA in the mitochondria of their muscle cells. Mitochondria produce energy for cells in the form of a molecule called adenosine triphosphate (ATP).

The study found that older people had not only a steady increase in the amount of damage suffered by their mitochondrial DNA but also a decrease in the amount of that DNA. Strikingly, the cumulative damage began as early as the 30s.

"Animal studies have shown a decline in DNA," Nair said. "What this study shows is that the decline begins in the fourth decade of life."

The report helps to settle a question in aging research, said Stephen Welle, a professor of medicine at the University of Rochester in New York , where Nair worked before moving to the Mayo Clinic.

"There has been some debate about whether or not, as we age, our muscles can make as much ATP as they did," Welle said. "Studies have found a kind of deficiency with normal aging, but most of those studies have been relatively small. This one has a large number of participants and makes a pretty convincing case that, with aging, there is a reduction in the amount of mitochondrial protein that is produced and a reduction in the ability to make ATP."

Nair now is working toward biological methods of reducing the decline in mitochondrial function. But even today, there's something anyone can do, he says --exercise.

"Aerobic exercise can increase ATP production," Nair said. "But we are asking whether there are other ways to stimulate the mitochondria. That is one focus of our research."

Any biotechnological intervention would be "some pretty high-tech stuff, like virally mediated transmission of DNA into muscles," Welle said, and there is no immediate prospect of such an intervention, no matter how welcome it might be to professional athletes.

The well-known recommendation -- "to keep in as good shape as possible by doing aerobic exercise" -- is the best advice available, Welle said.

"With aging, there is always some reduction in ATP production, no matter how hard you train. But the more you train, the better you maintain function," he added.