“Our experiments surprisingly indicate that muscle’s ability to adapt to the fed versus unfed state depends on mechanisms acting at the level of stem cells,” said Dr. Rudnicki. “These insights mean that perhaps one day we can develop drugs that target these mechanisms to alter the rate by which we age.”Intermittent fasting (or skipping meals) has often been reported to increase lifespan in various animals, but the observation that it also affects muscle stem cell function has been less well-studied. Now, a study from Dr. Michael Rudnicki’s team reveals the molecular links between fasting and muscle stem cell function for the first time.
The study shows that when muscles burn fat rather than sugar (as occurs during fasting), the body produces different metabolic by-products (more NAD+ and fewer acetyl groups) and these changes directly affect PAX7, the master regulator of muscle stem cells. Dr. Rudnicki’s team identified two genes that add and remove acetyl groups from PAX7, and show that these modifications alter muscle stem cell function and shift metabolism in skeletal muscle.
“Our experiments surprisingly indicate that muscle’s ability to adapt to the fed versus unfed state depends on mechanisms acting at the level of stem cells,” said Dr. Rudnicki, senior scientist and Director of the Regenerative Medicine Program at The Ottawa Hospital and a professor at the University of Ottawa. “These insights mean that perhaps one day we can develop drugs that target these mechanisms to alter the rate by which we age.”
Source: Nature Communications
Authors: Sincennes MC, Brun CE, Lin AYT, Rosembert T, Datzkiw D, Saber J, Ming H, Kawabe YI, Rudnicki MA.
Core resources: Bioinformatics, Flow Cytometry, Proteomics, StemCore
Funding: Ontario Research Fund, Ontario Institute for Regenerative Medicine, French Muscular Dystrophy Association, Canadian Institutes for Health Research, Canada Research Chair Program, US National Institutes for Health, Muscular Dystrophy Association, Stem Cell Network. All research at The Ottawa Hospital is also enabled by generous donors to The Ottawa Hospital Foundation.
The Ottawa Hospital is a leading academic health, research and learning hospital proudly affiliated with the University of Ottawa.
Media Contact
Jenn Ganton
613-614-5253
jganton@ohri.ca
