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How MTORC1 inhibition leads to longer telomeres

mtor sirt1 telomerase

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#1 sensei

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Posted 08 February 2022 - 05:32 PM


We know MTOR inhibits SIRT1. We know MTOR inhibition upregulates SIRT1 expression.

Apparently fasting creates iPSCs

"Fasting Mimicking Diet-Induced Pluripotency and Epigenetic Reprogramming in Hematopoietic Stem Cells during Aging"

And apparently multiple passes of iPSCs in the presence of enhanced SIRT1 expression lengthens telomeres

"Taken together, these results suggest that SIRT1 drives telomere elongation with passages of iPSCs by slowing down the degradation of c-MYC, which in turn promotes telomerase expression"
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#2 QuestforLife

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Posted 29 March 2022 - 01:41 PM

Obviously inhibiting mTOR will slow cell division leading to longer relative telomeres (compared to a control case). There is also the argument that a greater amount of telomerase protein does not necessarily lead to longer telomeres if cell division accelerates. But neither of these arguments is the exactly thrust of this study: basically if you can divert resources away from growth, stem cells will take that opportunity to replenish their numbers through symmetric division rather than renewing the body. A great example of this is the immortal planaria:

 

see: https://doi.org/10.1...mcr.2019.06.005

 

 

 

Downregulation of mTOR Signaling Increases Stem Cell Population Telomere Length during Starvation of Immortal Planarians

 

Reduction of caloric intake delays and prevents age-associated diseases and extends the life span in many organisms. It may be that these
benefits are due to positive effects of caloric restriction on stem cell function. We use the planarian model Schmidtea mediterranea, an
immortal animal that adapts to long periods of starvation by shrinking in size, to investigate the effects of starvation on telomere length.
We show that the longest telomeres are a general signature of planarian adult stem cells. We also observe that starvation leads to an
enrichment of stem cells with the longest telomeres and that this enrichment is dependent on mTOR signaling. We propose that one
important effect of starvation for the rejuvenation of the adult stem cell pool is through increasing the median telomere length in somatic
stem cells. Such a mechanism has broad implications for how dietary effects on aging are mediated at the whole-organism level.

 

 

I talked about it a little here

 


Edited by QuestforLife, 29 March 2022 - 01:45 PM.

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