Impaired Autophagy in the Aging of Stem Cell Populations

The cellular housekeeping mechanisms of autophagy act to recycle proteins and structures within the cell. Upregulation of autophagy appears to be a crucial part of the reason why the response to mild stresses - such as heat, cold, lack of nutrients, and toxins - can actually improve cell and tissue function. Certainly the practice of calorie restriction relies upon functional autophagy in order to extend healthy life span. Researchers here note that autophagy is important in the maintenance of the many stem cell populations throughout the body that are required for ongoing tissue maintenance. The characteristic impairment of autophagy in later life, taking place for reasons that are only partially explored, may make a sizable contribution to the loss of stem cell function that also takes place with aging.

Autophagy is a fundamental cell survival mechanism that allows cells to adapt to metabolic stress through the degradation and recycling of intracellular components to generate macromolecular precursors and produce energy. The autophagy pathway is critical for development, maintaining cellular and tissue homeostasis, as well as immunity and prevention of human disease. Defects in autophagy have been attributed to cancer, neurodegeneration, muscle and heart disease, infectious disease, as well as aging. While autophagy has classically been viewed as a passive quality control and general house-keeping mechanism, emerging evidence demonstrates that autophagy is an active process that regulates the metabolic status of the cell.

Adult stem cells, which are long-lived cells that possess the unique ability to self-renew and differentiate into specialized cells throughout the body, have distinct metabolic requirements. Research in a variety of stem cell types have established that autophagy plays critical roles in stem cell quiescence, activation, differentiation, and self-renew. While it appears that targeting autophagy to inhibit the autophagy-mediated cell survival properties in cancer stem cells may hold promise for anti-cancer therapy, the importance of autophagy in maintaining normal stem cell function suggest that inducing autophagy may have therapeutic potential for regenerative medicine. Certainly within the context of aging, stimulation of autophagy via genetic and pharmacological approaches in aged stem cells have improved their regenerative capacity and function.



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