Muscle Stem Cells Rejuvenated in Elderly Mice

Elderly mice were able to generate the cells necessary for muscle recovery after researchers rejuvenated their stem cell populations, a new study revealed. The work answers questions surrounding why the normal aging process accompanies a diminished ability to regain strength and mobility after muscle injury.

Writing in the journal Nature Medicine, Helen Blau of the Stanford University School of Medicine and her colleagues report that for the first time they were able to identify the process by which older muscle stem cell populations can be rejuvenated to function like younger cells.

"In the past, it's been thought that muscle stem cells themselves don't change with age, and that any loss of function is primarily due to external factors in the cells' environment," Blau said. "However, when we isolated stem cells from older mice, we found that they exhibit profound changes with age. In fact, two-thirds of the cells are dysfunctional when compared to those from younger mice, and the defect persists even when transplanted into young muscles."

"Our findings identify a defect inherent to old muscle stem cells," she added. "Most exciting is that we also discovered a way to overcome the defect. As a result, we have a new therapeutic target that could one day be used to help elderly human patients repair muscle damage."

Should the same rejuvenating effects be found true in human trials, it could be a great boon for elderly people needing treatment for muscle injuries.

"In mice, we can take cells from an old animal, treat them for seven days - during which time their numbers expand dramatically, as much as 60-fold - and then return them to injured muscles in old animals to facilitate their repair," Blau said.

Stanford Medicine postdoctoral scholar Benjamin Cosgrove, the study leader, said that their treatment does not turn back the clock for aging and dysfunctional stem cells, but rather that it takes still-functional stem cells from aging tissue and stimulates them so they begin dividing again.

"We were able to show that transplantation of the old treated muscle stem cell population repaired the damage and restored strength to injured muscles of old mice," Cosgrove said. "Two months after transplantation, these muscles exhibited forces equivalent to young, uninjured muscles. This was the most encouraging finding of all."

The researchers plan to continue their research using mice in hopes of gaining enough information on the process that it could perhaps be used in humans one day.

"If we could isolate the stem cells from an elderly person, expose them in culture to the proper conditions to rejuvenate them and transfer them back into a site of muscle injury, we may be able to use the person's own cells to aid recovery from trauma or to prevent localized muscle atrophy and weakness due to broken bones," Blau said. "This really opens a whole new avenue to enhance the repair of specific muscles in the elderly, especially after an injury. Our data pave the way for such a stem cell therapy."