Activation of aged muscle stem cells induces changes in DNA packaging that lead to expression of the gene Hoxa9. This reactivates embryonic signalling pathways, restricting the cells' ability to repair injured muscle. See Letter p.428
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Regulation of muscle stem cell fate
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Eliazer, S., Brack, A. Cause and consequence in aged-muscle decline. Nature 540, 349–350 (2016). https://doi.org/10.1038/nature20485
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DOI: https://doi.org/10.1038/nature20485
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Har Katcher
To state that blocking any of the signaling pathways Wnt, BMP?TGF-? and JAK?STAT etc. restores stem cell competence should mean that participation of some components of all pathways is required. To say, "or that the pathways are induced as a consequence of the stress caused by injury and lowering the levels of one pathway mitigates the stress response." implies that there is a graduated response to that stress stimulus, when there is only a binary response, the stem cell is competent or not.
So the question is why some regions of DNA are given restrictive marks with aging, and why the same stimulus in aged muscle stem cells (satellite cells) should produce a different response in old vs young tissue. The results of decades of experiments in heterochronic tissue transplantation, have definitively shown that aged muscle tissue transplanted into young animals develops youthful characteristics (including youthful tissue proliferation and youthful wound healing), while the reverse is true of young tissue transplanted into old animals. So the environment of the muscle satellite cells produces this effect and it can be reversed. Since blockage of any of the signaling pathways mentioned will restore the stem cells competence, one can assume that in young blood there are either molecules present that blocks one of more pathways, or insufficient activation of those pathways by young plasma as compared to old plasma (plasma from young or old animals). I think the scientific community is very closed-minded about the process of aging, deciding, without due cause, that it is a is cell autonomous process of random damage. With the single exception of altered cell signaling, even Lopez-Otin regards aging as occurring at the cellular level. I don't believe either of these to be true. What aging damages we see at the cellular through to organismic levels are stereotypical responses of organisms ranging from Caenorhabditis elegans to us. So far as being cell autonomous, in C. elegans at least, it is well known that the expressions of a gene in a single organ (brain or ovary or ova) can effect the lifespan of intestinal cells (their death is the usual lifespan limiter), and that lifespan length is fixed during development. Lifespan is a species characteristic that adapts an organism to its niche every bit as much as its mass, coloration, or breeding schedule; the normal life-history explanations of why short-lived organisms breed extensively,while long-lived organisms do not are but two examples of how species lifespan is affected by and affects species survival. The fact that the lifespan of an organism is a direct function of the its rate of loss as a young adult, (say by predation, before aging sets in), must mean that lifespan and aging are controlled. So to assume that aging and hence lifespan is random deterioration at the cellular level flies in the face of reality.