Skeletal muscle stem cells: origin, function and dysfunction in adult life

Z. Yablonka-Reuveni, K. Day, R. Almuly, G. Shefer
Department of Biological Structure, University of Washington School of Medicine, Seattle, WA

Our research focuses on the regulation of myogenic stem cell function in adult life. Our long-term goal is to identify means to ameliorate age-related muscle deterioration (sarcopenia). Sarcopenia is characterized by a decline in mass, strength, and endurance of skeletal muscles, and by fat accumulation between and within myofibers. Subtle muscle injuries that occur during routine muscle activity raise a continuous demand for functional myofiber repair throughout life. However, myogenic stem cell performance declines in old age and this decline can be a contributory factor to sarcopenia. We investigate satellite cells, classically defined tissue specific myogenic stem cells that reside beneath the myofiber basal lamina, as well as non-myogenic progenitors associated with the microvasculature that may contribute to myogenesis by myogenic reprogramming. We also investigate cellular and molecular mechanisms underlying adipogenic cell fate in skeletal muscles.

Our research approach is based on the view that muscle aging is not an isolated event that starts late in life, but rather a continuum of ongoing developmental biology processes that progress with life. The following aspects will be discussed: a) Mechanisms involved in supporting myogenic commitment and renewal of satellite cells. b) The potential of cells associated with the microvasculature, in particular the pericytes, to contribute to myofiber repair. Supported by NIH (AG013798 and AG021566).

Keywords: Skeletal muscle, Stem cell renewal, Satellite cells, Microvasculautre, Pericytes