Muscle Aging Linked to Stem Cell Overdrive

by GenNewsHighlights Staff ,  GenNewsHighlights | 2012-09-28

A protein that drives the generation of new muscle fibers from stem cells during development and after injury paradoxically also appears to be responsible for the gradual decline in our muscles’ ability to repair as we age. In vitro and in vivo studies by scientists at Massachusetts General Hospital (MGH), Kings College London, and Harvard Stem Cell Institute have found that the protein, fibroblast growth factor-2 (fgf2), is naturally overexpressed in aging muscles, and effectively sends muscle stem cells into overdrive, preventing them from replenishing their own populations and reducing their ability to keep muscles in tiptop condition.

A rare population of muscle stem cells—also called satellite cells—is found in every skeletal muscle. The cells reside in a dormant, or quiescent state, but can be mobilized rapidly to differentiate into new muscle cells following injury, and also generate a replacement pool of stem cells that revert back to a healthy dormant state until next required.

Initial studies in mice by scientists at MGH showed that the numbers of these dormant satellite cells in muscle decline with age, and the cells also lose markers of quiescence and self-renewal and gain markers of differentiation and apoptosis. In their hunt for factors expressed in the muscle fiber that might trigger this change in satellite cells, they found that fgf2—which is one of the natural triggers for stem cell mobilization and differentiation—are markedly elevated in the niche, or microenvironment, that surrounds stem cells in aging muscle.

Critically, in vitro and in vivo mouse studies demonstrated that the high levels of fgf2 in aged muscle effectively kicks the stem cells out of their quiescent state and triggers them to proliferate and differentiate, preventing the replenishment of the pool of quiescent stem cells, and effectively leading to a depleted satellite cell population and thus reduced ability of muscle to regenerate.



chatno

PlacidWay

Support