Study explains why muscles weaken with age

For those people who hope to run long into their old age, new research out of the U.S. may offer some hope to help keep those muscles strong no matter how old you are.

Researchers at Columbia University Medical Center say they have discovered the biological mechanism behind age-related loss of muscle strength and identified a drug that may help reverse this process. Their findings were published in the Aug. 2 online edition of Cell Metabolism.

As people age, skeletal muscles tend to wither and weaken, a phenomenon known as sarcopenia. Sarcopenia, which begins to appear around age 40 and accelerates after 75, is a major cause of disability in the elderly. Exercise can help counter the effects of age-related muscle loss, but there are no other established treatments.

According to the new study, conducted in mice, sarcopenia occurs when calcium leaks from a group of proteins in muscle cells called the ryanodine receptor channel complex. These leaks then trigger a chain of events that ultimately limits the ability of muscle fibres to contract, says study leader Dr. Andrew R. Marks. In fact, it’s very like muscular distrophy.

“This is a completely new concept — that the damage that occurs in aging is very similar to what happens in muscular dystrophy,” says Dr. Marks, “thus as we age we essentially develop an acquired form of muscular dystrophy.”

Both the aging process and the genetic defect responsible for muscular dystrophy cause an increase in the production of oxygen free radicals, highly reactive and harmful molecules. “Our data suggest that this sets up a vicious cycle, in which the free radicals cause ryanodine receptors to leak calcium into the cell. The calcium poisons mitochondria — organelles that power the cell — leading to the release of even more free radicals. This, in turn, causes more calcium leakage. With less calcium available for contraction, the muscles get weaker,” says Dr. Daniel C. Andersson, another author of the study.

The study also points to a possible therapy for sarcopenia: an experimental drug called S107, developed by Dr. Marks and his colleagues. The drug acts to essentially prevent this calcium leakage.

In the study, 24-month-old mice (roughly the equivalent of 70-year-old humans) were given S107 for four weeks. The mice showed significant improvements in both muscle force and exercise capacity, compared with untreated controls. “The mice ran farther and faster during voluntary exercise,” says Dr. Andersson. “When we tested their muscles, they were about 50 per cent stronger.” The drug had no effect on younger mice with normal ryanodine receptors.