Cell-signaling pathway that plays key role in age-related muscle loss identified

A new study 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.

According to Bradley Olwin from University of Colorado Boulder, 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, Olwin said.

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.

"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," Olwin said.

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, the researcher said.

The study was published in the journal Nature Medicine.