Aged Mice : In Clinical Trials
Aged Mice : In Clinical Trials
Blocking the activity of a single protein in old mice for one month restores mass and strength to the animals' withered muscles and helps them run longer on a treadmill, according to a study by researchers at the Stanford University School of Medicine. Conversely, increasing the expression of the protein in young mice causes their muscles to atrophy and weaken.
The old mice are about 15% to 20% stronger after one month of treatment, and their muscle fibers look like young muscle. Considering that humans lose about 10% of muscle strength per decade after about age 50, this is quite remarkable."
The protein hasn't previously been implicated in aging. The researchers show that the amount of the protein, called 15-PGDH, is elevated in old muscle and is widely expressed in other old tissues. Experiments they conducted in human tissue raise hopes for a future treatment for the muscle weakness that occurs as people age.
Blau, the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Laboratory for Stem Cell Biology, is the senior author of the study, which will be published online Dec. 10 in Science. Senior scientist Adelaida Palla, PhD, is the lead author.
Muscle loss during aging is known as sarcopenia, and it accounts for billions of dollars of health care expenditures in the United States each year as people lose the ability to care for themselves, experience more falls and become increasingly less mobile. It is due to changes in muscle structure and function: The muscle fibers shrink and the number and function of the cellular powerhouses known as mitochondria dwindle.
Blau and her colleagues have long been interested in understanding muscle function after muscle injury and in diseases like Duchenne muscular dystrophy. Previously, they found that a molecule called prostaglandin E2 can activate muscle stem cells that spring into action to repair damaged muscle fibers.
"We wondered whether this same pathway might also be important in aging," Blau said. "We were surprised to find that PGE2 not only augments the function of stem cells in regeneration, but also acts on mature muscle fibers. It has a potent dual role."
Prostaglandin E2 levels are regulated by 15-PGDH, which breaks down prostaglandin E2. The researchers used a highly sensitive version of mass spectrometry, a method for differentiating closely related molecules, to determine that compared with young mice, the 15-PGDH levels are elevated in the muscles of older animals, and the levels of prostaglandin E2 are lower.
They found a similar pattern of 15-PGDH expression in human muscle tissues, as those from people in their 70s and early 80s expressed higher levels than those from people in their mid-20s.
Regards
John George