Old muscle stem cells experimentally returned to youth

Researchers at the University of California, Berkeley have found molecular pathways that human muscle stem cells rely on to repair damaged muscle. These pathways are active in younger people but less active in older people, explaining why muscles repair more slowly with age. The group found that younger volunteers had double the number of regenerative muscle stem cells in their thigh muscles compared to older volunteers. After two weeks in a leg cast, both groups began exercise routines to rebuild muscle. During this phase, the older volunteers had four times fewer muscle stem cells and rebuilt muscle more slowly. The researchers said that the poor response wasn’t the fault of the older stem cells. Instead, signals in the aging muscle and blood locked the stem cells in an inactive state. From their work in mice, the researchers knew that proteins present in the muscle surrounding the stem cells helped these cells respond to distress signals from the injured tissue. In the human cells, they found a protein called MAPK that interprets these distress signals and triggers the muscle stem cells to begin the repair process. Young people have high levels of MAPK and older people have low levels of MAPK, providing one explanation for the older volunteers’ poor response to exercise. In a lab dish, the group found that by artificially blocking MAPK in young muscle stem cells they could make young cells respond like older cells in a matter of days. The reverse was also true. Amplifying MAPK in older muscle stem cells in a lab dish rejuvenated the older cells. This work is an important step in verifying results from mouse stem cell aging studies in humans. The researchers hope their work could lead to therapies for muscle diseases and help older people to remain active, build stronger muscles and recover from injury.

EMBO Molecular Medicine: September 30, 2009
CIRM funding: Irina Conboy (RN1-00532-1), Morgan Carlson (T1-00007)

Related Information: Press Release, University of California, Berkeley

A.A.

Aging Muscles Inhibit Stem Cells, Prevent Repair

Researchers at UC, Berkeley identified a signaling molecule that interferes with the ability of older skeletal muscle to regenerate. After injury, adult skeletal muscle regenerates by activating muscle stem cells that fuse with the existing muscle cells to repair the damage. This ability to regenerate diminishes with age, not because of a decline in the number of resident stem cells, but because stem cells in the older muscle don’t respond when damage occurs. It turns out that older muscles release molecules that actively inhibit the resident stem cells. In this study, the team identified one of those molecules and showed that interfering with that molecule’s function restores the ability of muscle in older mice to regenerate after injury. This research illustrates the potential for recruiting adult resident stem cells in tissue repair.

Nature: June 15, 2008.
CIRM funding: Morgan Carlson (T1-00007)

Related Information: Press release, Berkeley Stem Cell Center