The Age-Related Decline of Mitophagy as a Contributing Cause of Stem Cell Dysfunction

Stem cells support the maintenance of tissue by delivering a regular supply of daughter somatic cells to replace losses. Different tissues turn over at different rates, but the contribution of stem cells is vital. Stem cell function declines with age, however, and a slow spiral into frailty and organ failure follows as a consequence. In the most studied populations, this loss of stem cell function is largely a matter of declining activity in response to the age-damaged environment. Put into a youthful environment, stem cells from old tissues can still perform well.

Researchers here draw a line between declining mitophagy and declining stem cell function. Mitophagy is the specialized form of autophagy that removes damaged mitochondria in cells. Mitophagy falters in cells in old tissue due to a range of complicated issues that appear quite distant from the root causes of aging. Necessary proteins are produced in too low an amount, mitochondrial dynamics change, and the component parts of the autophagic system all suffer their own similar problems. Dysfunctional mitophagy leads to dysfunctional mitochondria, and that in turn has a negative impact on stem cell activity.

Mitophagy is a specific autophagic phenomenon in which damaged or redundant mitochondria are selectively cleared by autophagic lysosomes. A decrease in mitophagy can accelerate the aging process. Mitophagy is related to health and longevity and is the key to protecting stem cells from metabolic stress damage. Mitophagy decreases the metabolic level of stem cells by clearing active mitochondria, so mitophagy is becoming increasingly necessary to maintain the regenerative capacity of old stem cells.

Stem cell senescence is the core problem of tissue aging, and tissue aging occurs not only in stem cells but also in transport amplifying cell chambers and the stem cell environment. The loss of the autophagic ability of stem cells can cause the accumulation of mitochondria and the activation of the metabolic state as well as damage the self-renewal ability and regeneration potential of stem cells. However, the claim remains controversial.

Mitophagy is an important survival strategy against nutrient deficiency and starvation, and mitochondrial function and integrity may affect the viability, proliferation, and differentiation potential, and longevity of normal stem cells. Mitophagy can affect the health and longevity of the human body, so the number of studies in this field has increased, but the mechanism by which mitophagy participates in stem cell development is still not fully understood.

Link: https://doi.org/10.1186/s13287-021-02520-5

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