CU-Boulder Stem Cell Research May Point to New Methods of Mitigating Muscle Loss

Boulder, CO (PRWEB) February 16, 2014

New findings on why skeletal muscle stem cells stop dividing and renewing muscle mass during aging points up a unique therapeutic opportunity for managing muscle-wasting conditions in humans, says a new University of Colorado Boulder study.

According to CU-Boulder Professor Bradley Olwin, the loss of skeletal muscle mass and function as we age can lead to sarcopenia, a debilitating muscle-wasting condition that generally hits the elderly hardest. The new study indicates that altering two particular cell-signaling pathways independently in aged mice enhances muscle stem cell renewal and improves muscle regeneration.

One cell-signaling pathway the team identified, known as p38 MAPK, appears to be a major player in making or breaking the skeletal muscle stem cell, or satellite cell, renewal process in adult mice, said Olwin of the molecular, cellular and developmental biology department. Hyperactivation of the p38 MAPK cell-signaling pathway inhibits the renewal of muscle stem cells in aged mice, perhaps because of cellular stress and inflammatory responses acquired during the aging process.

The researchers knew that obliterating the p38 MAPK pathway in the stem cells of adult mice would block the renewal of satellite cells, said Olwin. But when the team only partially shut down the activity in the cell-signaling pathway by using a specific chemical inhibitor, the adult satellite cells showed significant renewal, he said. We showed that the level of signaling from this cellular pathway is very important to the renewal of the satellite cells in adult mice, which was a very big surprise, said Olwin.

A paper on the subject appeared online Feb. 16 in the journal Nature Medicine.

One reason the CU-Boulder study is important is that the results could lead to the use of low-dose inhibitors, perhaps anti-inflammatory compounds, to calm the activity in the p38 MAPK cell-signaling pathway in human muscle stem cells, said Olwin.

The CU-Boulder research team also identified a second cell-signaling pathway affecting skeletal muscle renewal a receptor known as the fibroblast growth factor receptor-1, or FGFR-1. The researchers showed when the FGFR-1 receptor protein was turned on in specially bred lab mice, the renewal of satellite cells increased significantly. We still dont understand how that particular mechanism works, he said.

Another major finding of the study was that while satellite cells transplanted from young mice to other young mice showed significant renewal for up to two years, those transplanted from old mice to young mice failed. We found definitively that satellite cells from an aged mouse are not able to maintain the ability to replenish themselves, Olwin said. This is likely one of the contributors to loss of muscle mass during the aging process of humans.

Co-authors included first author and CU-Boulder postdoctoral researcher Jennifer Bernet, former CU-Boulder graduate student John K. Hall, CU-Boulder undergraduate Thomas Carter, and CU-Boulder postdoctoral researchers Jason Doles and Kathleen Kelly-Tanaka. The National Institutes of Health and the Ellison Medical Foundation funded the study.

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CU-Boulder Stem Cell Research May Point to New Methods of Mitigating Muscle Loss