Blocking an aging-related enzyme may restore muscle strength

As people age, their muscles tend to dwindle and weaken, especially with lack of use. With continued muscle loss, daily tasks are harder to perform and the risk of falling increases. One research team is teasing apart what’s behind this muscle loss by focusing on an enzyme associated with aging, which they’ve named a “gerozyme.”

The enzyme is 15-hydroxyprostaglandin dehydrogenase, or 15-PGDH. It breaks down a signaling compound called prostaglandin E2. That compound activates the proliferation of muscle stem cells, regenerating damaged muscles.

Stem cell biologist Helen Blau of Stanford University School of Medicine and colleagues previously found that blocking 15-PGDH in old mice restored their withered muscles and improved their strength after a month of treatment. On the flip side, young mice lost muscle and became weaker after their levels of this enzyme were increased for a month.

Blau’s team has now found that 15-PGDH accumulates in the muscles of old mice as the connections that allow communication between muscles and nerves are lost, another consequence of aging. Treating old mice for one month with a drug that inhibits 15-PGDH restored these connections, called synapses, between muscle fibers and motor nerve cells, and boosted the animals’ strength, the team reports in the Oct. 11 Science Translational Medicine. Those synapses are how the brain directs muscles to move.

The findings suggest that blocking the gerozyme 15-PGDH may be a way to help recover strength that has diminished due to nerve injuries, motor nerve cell diseases or aging.