Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis.
The regenerative potential of skeletal muscle declines with age, and this impairment is associated with an increase in tissue fibrosis. We show that muscle stem cells (satellite cells) from aged mice tend to convert from a myogenic to a fibrogenic lineage as they begin to proliferate and that this conversion is mediated by factors in the systemic environment of the old animals. We also show that this lineage conversion is associated with an activation of the canonical Wnt signaling pathway in aged myogenic progenitors and can be suppressed by Wnt inhibitors. Furthermore, components of serum from aged mice that bind to the Frizzled family of proteins, which are Wnt receptors, may account for the elevated Wnt signaling in aged cells. These results indicate that the Wnt signaling pathway may play a critical role in tissue-specific stem cell aging and an increase in tissue fibrosis with age.
Brack
Andrew S
AS
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Conboy
Michael J
MJ
Roy
Sudeep
S
Lee
Mark
M
Kuo
Calvin J
CJ
Keller
Charles
C
Rando
Thomas A
TA
D000375:Aging / Q000502:physiology*; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005355:Fibrosis / Q000473:pathology*; D051157:Frizzled Receptors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010227:Parabiosis; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
D051157:Frizzled Receptors; D051153:Wnt Proteins