Stemness maintenance in skeletal muscle : a focus on aging
Year: 2015
Type: dissertation
Abstract: During aging, muscle stem cell regenerative function declines, being maximal at advanced geriatric age, due to a quiescence-to-senescence transition. How quiescence is maintained over long periods of time remains largely unknown. Here we demonstrate that basal autophagy is indispensable for muscle stem cell quiescence maintenance. Physiological failure of autophagy in aging muscle stem cells or forced genetic impairment in young cells causes senescence entry by loss of proteostasis and increased ROS, resulting in numerical and functional stem cell decline. Autophagy reestablishment reverses senescence and restores regenerative functions in geriatric muscle stem cells from mouse and humans. Furthermore, we also show that FoxO transcription factors are critical for muscle stem cell quiescence through repression of the myogenic differentiation program. Indeed, FoxO deficiency impairs postnatal establishment and life maintenance of the stem cell pool by allowing inappropriate differentiation. These findings uncover new regulatory mechanisms decisive for homeostatic and regenerative functions of muscle stem cells.
Author: Laura García‐Prat
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2848379168