Nature: Autophagy and Stem Cell Fate

 Journal Title: Nature Date: 2016-01-08

DOI: 10.1038 / nature16187 Author: Pompeu Fabra University

Researchers from the University of Pompeu Fabra in Spain published an article in this issue of Nature and pointed out that autophagy is the key to maintaining the stemness of muscle satellite cells.

Autophagy is a process by which cells transport damaged, denatured or senescent proteins and organelles to lysosomes for digestion and degradation. It is very conservative in evolution (from yeast to humans).

The regeneration capacity of skeletal muscle depends on long-lived muscle stem cells (called satellite cells). These cells are generally in a resting state, activated when the tissue is damaged, generating muscle fibers or performing self-renewal. The resting state is a simple way to maintain the skeletal muscle stem cell population.

The regenerative function of muscle stem cells gradually declines in the aging process, and this decline reaches its peak in the final stage of life. Because of this, the elderly are prone to suffer from sarcopenia, which is an age-related loss of skeletal muscle mass and function.

Researchers conducted in-depth studies on physiologically aging mice. Studies have shown that muscle stem cells preserve their strength by maintaining organelles and protein homeostasis, which is an important quality control mechanism. Muscle stem cells in the resting state continue to undergo basic autophagy, which will weaken during the aging process. .

Studies have shown that aging skeletal muscle cannot maintain the resting state of stem cells. As we age, the number of muscle stem cells gradually decreases and their function declines. In senile muscle attenuation syndrome, satellite cells change from a resting state to an aging state.

In physiologically aging satellite cells or autophagy-deficient young cells, the failure of autophagy will lead to the loss of protein homeostasis, mitochondrial dysfunction and increased oxidative stress, and the accumulation of corresponding toxic wastes will eventually make the satellite cells enter a state of aging. Further studies have shown that rebuilding autophagy in old satellite cells can reverse aging and restore its regenerative function.

This study tells us that autophagy is a decisive regulator of stem cell fate. People can develop new therapies on this basis to promote muscle regeneration in muscle attenuation signs.