On Autophagy in Stem Cells
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Autophagy is the collection of housekeeping processes that aim to keep a cell in good shape - free from damaged components and unwanted metabolic byproducts. More autophagy is a good thing, and boosted levels of autophagy seem to be involved in many of the methods found to extend life in laboratory animals.

By way of following up on a post from yesterday on apparent damage repair and reversal of some markers of aging in induced pluripotent stem cells (iPSCs), I thought I'd direct your attention to a recent open access paper on the involvement of autophagy in stem cell biology. Perhaps much of the seeming cellular rejuvenation brought about through passing old cell lineages through an induced pluripotent stage has to do with greatly enhanced autophagy:

The implication of autophagy in the maintenance of stemness adds a new layer of control on stem cell activity. Firstly, autophagy may serve as a critical mechanism for the regulation of self-renewal and differentiation. Indeed, stem cells require especially efficient protein turnover to eliminate unwanted proteins, which may otherwise accumulate and impair identity and function. Both autophagy and the ubiquitin-proteasome system (UPS) are important for protein quality control and the maintenance of cellular homeostasis, and they cooperate to regulate cellular aging.

Dysfunction or decrease of the stem cell pools is typical of physiological and pathological aging; it would be therefore interesting to determine how these two protein degradation pathways are coordinated in the regulation of stem cell homeostasis, and how the dysregulation of autophagy in stem cells is linked to aging and degenerative diseases. Additionally, the involvement of autophagy in somatic reprogramming suggests a new methodological basis for developing strategies to efficiently generate iPSCs. Finally, increased autophagy may enable cells to overcome the cellular senescence barrier by remodelling the cell cycle machinery or by promoting the turnover of the 'senescent' subcellular architecture.

In summary, the study of the interplay between autophagy and cell stemness will not only increase our understanding of the mechanisms and pathways through which autophagy contributes to stem cell maintenance and differentiation, but also enhance our knowledge of the roles of autophagy in human development, aging, and various degenerative diseases. Stem cell rejuvenation and function and large-scale production of high quality transplantable materials through active manipulation of autophagic pathways using small molecules and/or targeted genome-editing technology may be more than a dream.

Link: http://onlinelibrary.wiley.com/doi/10.1002/emmm.201201999/full

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