Hallmark of Aging 9 - Stem Cell Exhaustion

July 07, 2024

Hallmark of Aging 9 - Stem Cell Exhaustion


Aging is associated with a gradual degradation of stem cells to replace the worn-out cells in any particular organ. Each organ appears to have its own source of stem cells and its mechanisms and means of eliciting their revival. Injury is a frequent cause of stem cell regeneration demand. Because it is the site of frequent injury, the skin has multiple cells that can be recruited to become stem cells. Muscles, on the other hand, appear to have a predetermined hierarchy of stem cell regeneration. Most organs have a much slower regeneration cycle as they don't suffer the frequent injury cycle of the skin. Tissue injury results in de-differentiation of many cell types. By way of example, in the intestine, brain, and lung, injury induces de-differentiation of non-stem cells, which proceed to reactivate normally silent embryonic transcription programs. One doesn't think of the lung being injured until you imagine sitting over an open fire trying to cook meat while hyenas prowl just beyond the shadows. You breathe in all that smoke and injure your lungs, but you keep the hyenas at bay with the fire.


By reacting to injury you have also acquired the plasticity needed for tissue repair. Your mature cells have "regressed" and become less mature, differentiating back into stem cells. Four key enzyme systems control all this: OCT4, SOX2, KLF4, and MYC (OSKM). You have heard of this as recent news reports talk about taking ordinary skin cells and using them to create stem cells, even eggs for starting an organism from scratch.


This differentiation back to a more primitive cell type doesn't erase the epigenetic markers or the Hayflick clock completely, suggesting that differentiation and rejuvenation are linked. But much does not re-establish of the erased aging-associated changes and therefore resets the epigenome and transcriptome to a younger state. Something about injury establishes a younger state. Hmm, is that the benefit of weight-bearing exercise? Slight injury causing younger regeneration.


The problem with aging is that this all just plain slows down. You can only bench-press your way out of trouble for so long.


www.What will Work for me? I look at the age spots on my hands and forearms and consider all the sun damage my skin has endured. I'm not in the market for fertility treatments, but the idea of setting back the epigenetic clock is intriguing. I'm glad there are lots of researchers all over the world working on this.


References:Cell, Development, Cell Stem Cell, Cell, Technology Networks, Science,


Pop Quiz


1. What is stem cell exhaustion? Answer: The inexorable winding down of the ability to repair after injury.


2. Where can you see this process playing out on your own body? Answer: How long does it take for the bruise on your arm to fade, the cut on your arm to heal?


3. Is there some unexpected benefits to exploring tissue repair? Answer: Yes, we now understand how to turn back the differentiation of mature cells to capture the "pluripotential" of stem cells.


4. How far back? Answer: All the way to the original stem cell, the egg.


5. Are researchers sharing everything they know on this topic? Answer: Are you kidding? This is big-buck territory because of the fertility industry. To discover and profit from findings is a high bar to overcome.

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