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Study: NMN Stabilizes telomeres, improves liver function, could treat age-related disease (mice)

nmn telomere

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#1 Phoebus

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Posted 28 March 2019 - 04:09 PM


 

 

Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease
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Published: March 28, 2019DOI:https://doi.org/10.1...met.2019.03.001
 
 
Highlights
  • Telomere dysfunction downregulates sirtuins in the liver in a p53-dependent manner
  • p53 represses sirtuins through transcriptional and post-transcriptional mechanisms
  • Telomere dysfunction is linked to a steep decline in NAD(+) upon additional damage
  • NAD(+) supplementation stabilizes telomeres and improves liver fibrosis
Summary
Telomere shortening is associated with stem cell decline, fibrotic disorders, and premature aging through mechanisms that are incompletely understood. Here, we show that telomere shortening in livers of telomerase knockout mice leads to a p53-dependent repression of all seven sirtuins. P53 regulates non-mitochondrial sirtuins (Sirt1, 2, 6, and 7) post-transcriptionally through microRNAs (miR-34a, 26a, and 145), while the mitochondrial sirtuins (Sirt3, 4, and 5) are regulated in a peroxisome proliferator-activated receptor gamma co-activator 1 alpha-/beta-dependent manner at the transcriptional level. Administration of the NAD(+) precursor nicotinamide mononucleotide maintains telomere length, dampens the DNA damage response and p53, improves mitochondrial function, and, functionally, rescues liver fibrosis in a partially Sirt1-dependent manner. These studies establish sirtuins as downstream targets of dysfunctional telomeres and suggest that increasing Sirt1 activity alone or in combination with other sirtuins stabilizes telomeres and mitigates telomere-dependent disorders.

https://www.cell.com...4131(19)30129-9

 

 

article on this study


https://www.bcm.edu/...related-disease

 

 


Edited by Phoebus, 28 March 2019 - 04:09 PM.

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#2 OP2040

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Posted 28 March 2019 - 06:53 PM

LoL, this is sure to get MickeDC riled.


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#3 ledgf

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Posted 28 March 2019 - 08:55 PM

Mice don't shut down telomerase in their cells... no rodent or lagomorph does, IIRC. 

And I DO RC, because I worked on those cells at Shay-Wright ;)

https://www.ncbi.nlm...les/PMC3387546/


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#4 able

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Posted 28 March 2019 - 11:43 PM

LoL, this is sure to get MickeDC riled.

 Haven't you noticed?  MikeDC only lasted one day after return from his last suspension, before he got booted again.  We have another month or two of relative peace before his next return.


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#5 male_1978

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Posted 29 March 2019 - 07:31 AM


“Telomere shortening signaled the cell to reduce the production of sirtuins. This observation indicates that telomeres regulate sirtuins.”

...

“It’s important to keep in mind that telomere length can also affect cancer growth. Having shorter telomeres would set cancer cells on a path to self-destruction, but keeping their telomeres long would likely allow them to continue proliferating,”

 

So are we messing around with the emergency break here? I am unsure what to think about this with respect to long term effects.

 



#6 ledgf

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Posted 29 March 2019 - 12:25 PM

So are we messing around with the emergency break here? I am unsure what to think about this with respect to long term effects.

The "brake"? Short answer, no. (I worked in the Shay-Wright lab from 2001-5, and have followed the telomerase story since). 

There are several long-lived animals that don't let their telomeres shorten at all (Blanding's Turtle, some of the albatross-niche birds). You're more likely to get cancer from a cell division gone wrong in a cell with short telomeres. 

Read Josh Mitteldorf's and Steve Austad's books on aging theory... aging is programmed. 


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#7 OP2040

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Posted 29 March 2019 - 12:39 PM

There seem to be multiple ways of dealing with telomeres for animals that have longer lifespans.  There are those that do keep the telomerase rockin long past when we do.  There are those whose telomere shortening just don't tick down that fast.  There are others for which the stability of the telomere, for example shelterin expression, is much better. 

 

There is always more than one way to do things in biology.  Some animals with longevity don't bother with the telomere pathway at all.  I believe it's naked mole rats that don't have very impressive telomere dynamics.  Their strategy is more about cellular and intercellular stability.

 

Of course, we never get far in any thread about regenerative medicine without the big C scare.  Lets be very clear here, all regenerative pathways are correlated with cancer, for what should be obvious reasons.  This does not mean they cause cancer.  Nor does it mean that shutting down regenerative pathways cures cancer.  In current cancer medicine, this is a major strategy that has been tried for almost every regenerative pathway.  Shut down DNA repair is just one example.  I don't see a cancer cure from that, nor even minimal progress.  We have to get past this bad, sloppy science.  Longer telomeres do not cause cancer, nor do short telomeres protect against cancer.  The closest answer that we have as to what causes cancer is immunosenescence. 


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#8 Phoebus

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Posted 29 March 2019 - 04:25 PM

The "brake"? Short answer, no. (I worked in the Shay-Wright lab from 2001-5, and have followed the telomerase story since). 

There are several long-lived animals that don't let their telomeres shorten at all (Blanding's Turtle, some of the albatross-niche birds). You're more likely to get cancer from a cell division gone wrong in a cell with short telomeres. 

Read Josh Mitteldorf's and Steve Austad's books on aging theory... aging is programmed. 

 

So, do you think NR/NMN could possibly reprogram cells? 

 

Do you consider stabilizing the chromosome ends to be a type of reprogramming? 






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