Autophagy maintains stemness by preventing senescence.

Area of Science:

• Muscle stem cell biology
• Cellular senescence
• Autophagy and aging

Background:

• Muscle stem cell regenerative function declines with age, progressing to senescence.
• The mechanisms maintaining stem cell quiescence and preventing senescence remain unclear.
• Autophagy, a cellular degradation process, is known to decline with age.

Purpose of the Study:

• To investigate the role of basal autophagy in maintaining muscle stem cell quiescence.
• To determine if autophagy failure contributes to age-related stem cell senescence.
• To explore the potential of autophagy restoration for muscle regeneration.

Main Methods:

• Studied autophagy-deficient aged mice and genetically modified young mice.
• Assessed stem cell function, senescence markers, proteostasis, mitochondrial function, and oxidative stress.
• Investigated the effects of re-establishing autophagy in aged satellite cells.

Main Results:

• Basal autophagy is essential for maintaining muscle stem cell quiescence.
• Autophagy failure induces senescence via proteostasis loss, mitochondrial dysfunction, and oxidative stress.
• Restoring autophagy reverses senescence and restores regenerative capacity in aged satellite cells.
• Autophagy decline is observed in human geriatric satellite cells.

Conclusions:

• Autophagy is a critical regulator of muscle stem cell fate and function.
• Targeting autophagy presents a therapeutic strategy for age-related muscle decline and sarcopenia.