Editors' ChoiceStem Cells

Running makes old stem cells act young

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Science Translational Medicine  06 May 2020:
Vol. 12, Issue 542, eabb7092
DOI: 10.1126/scitranslmed.abb7092

Abstract

Voluntary wheel running restores aged muscle stem cells’ ability to activate and repair tissue after injury in mice.

Aging is a progressive malfunctioning of homeostasis and a primary risk factor for multiple diseases, including osteoporosis, Alzheimer’s, hypertension, skeletal muscle wasting (sarcopenia), as well as cancers. Exercise has long been recognized to provide health benefits and combat age-associated pathologies, but molecular mechanisms that confer these responses have remained elusive. Skeletal muscle is the primary tissue responsible for contractile movements, but skeletal muscle atrophies in aging. This degeneration is in part due to the loss of numbers and function of skeletal muscle stem cells (SMuSCs). Brett and co-workers used short-term (3 weeks) voluntary wheel running as a stimulus to rejuvenate skeletal muscle stem cells (SMuSCs) in aged mice (20 to 22 months). The authors observed rescue of defects in activation in aged SMuSCs through injury recovery and transplantation assays, which diminished one week after exercise ceased and SMuSCs reverted to aged behavior. Investigation of the molecular signatures that conferred benefits to exercised SMuSCs revealed increases in cyclin D1, and genetic reduction of cyclin D1 in young SMuSCs caused cells to behave similarly to aged SMuSCs. Conversely, genetic rescue of cyclin D1 in aged SMuSCs attenuated activation defects, which the authors observed was through inhibition of transforming growth factor–β signaling.

The identification of molecular factors that confer benefits to tissue resident stem cells is exciting because there are no therapies for sarcopenia. Additional studies are needed to determine how other cell types in skeletal muscle are affected by exercise and how SMuSCs change their communication with other tissues during other forms of exercise such as resistance training. Given that the aging population is increasing, these results may offer a promising strategy for prevention of sarcopenia and other muscle-wasting conditions.

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