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Short Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish

telomerese aging

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#1 GreenPower

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Posted 13 February 2016 - 05:21 AM


Interesting study in PLOS Genetics on whether tissue specific telomere shortening triggers systemic aging signals.

 

Abstract
Telomeres shorten with each cell division and telomere dysfunction is a recognized hallmark of aging. Tissue proliferation is expected to dictate the rate at which telomeres shorten. We set out to test whether proliferative tissues age faster than non-proliferative due to telomere shortening during zebrafish aging. We performed a prospective study linking telomere length to tissue pathology and disease. Contrary to expectations, we show that telomeres shorten to critical lengths only in specific tissues and independently of their proliferation rate. Short telomeres accumulate in the gut but not in other highly proliferative tissues such as the blood and gonads. Notably, the muscle, a low proliferative tissue, accumulates short telomeres and DNA damage at the same rate as the gut. Together, our work shows that telomere shortening and DNA damage in key tissues triggers not only local dysfunction but also anticipates the onset of age-associated diseases in other tissues, including cancer.

 


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#2 Logic

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Posted 14 February 2016 - 03:21 PM

And the gut is what astragalus etc has to 'pass through'... or does it?

The gut is the barrier between the rest of you and sudden death by septicemia and becomes more and more leaky with age...
Also look at the toxins produced in and leaked through the gut due to our almost total disinterest in the type of bacteria in it.

These all lead to inflammation and an increase in NF-kB and co.

Note that almost all Telomerase activators downregulate NF-kB and co.

Probably by making the gut less leaky, more than anything else..?

Then there's the little nugget of info on the old age type epigenetic changes caused by only slightly short telomeres that seems to fly right over most.

 

Talk about not seeing the woods for the trees!

:)


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#3 Rocket

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Posted 19 February 2016 - 02:08 PM

If you note, in this literature and others, the comments are always "short" telomeres, not ZERO length telomeres.  I'm not a cell biologist, but I think there is sufficient evidence that extending telomere length in *all* the bodies tissues would go a long, long way to elimination much of the decimation to the body that comes with the years.  I don't believe the only thing to telomeres is increasing the Hayflick limit in cell divisions! 

 

I also wonder about the biolavailability of the oral telomerase supplements, and even if it a small amount that survives the digestive process, I wonder their effectiveness in activating telomerase in all the of the tissues necessary for a true "anti aging" benefit.


Edited by Rocket, 19 February 2016 - 02:14 PM.


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#4 Logic

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Posted 19 February 2016 - 05:11 PM

To whoever disagreed:

I am here to learn, so please feel free to post your disagreement so we can talk about it!   :)

To elaborate on my gut hypothesis:

The gut has a very high cell turnover so it stands to reason that its telomeres are shorter than most.
Now all the astragalus etc we take has to pass through the gut to get into the rest of us.
So it's altogether possible that it absorbs and benefits more from the astragalus etc than the rest of our cells do, leading to longer telomeres in the new gut cells and a less leaky gut.

 

Now as the ever more leaky gut leads to inflammation and upregulated NF-kB and almost all telomerase activators downregulate NF-kB;  it stands to reason that quite possibly a less leaky gut pays a large part in the telomerase activation seen elsewhere from these supps.

 

Astragalus also upregulates the immune system and low level chronic infection/s are another reason for increased NF-kB etc...

 

The other is AGEs and the accumulation of iron and copper etc.

 

Some links proving and expanding upon the statements in my previous post:

http://www.longecity...ndpost&p=716857

http://www.longecity...and-telomerase/

 

 

 

 


Edited by Logic, 19 February 2016 - 05:16 PM.

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#5 niner

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Posted 19 February 2016 - 10:06 PM

Telomeres shorten for other reasons beside cell division.  Primary among these is oxidative damage.  There may be high turnover in the gut, but there is not high turnover in muscle, however telomeres still shorten there.  That might be oxidative damage due to muscular exertion.   Telomerase acts preferentially on critically short telomeres, so if you do manage to induce some telomerase activity, it will probably not do you much good unless you have some short telomeres.  Of course, in an aged individual, there will probably be a non-trivial number of critically short telomeres, at least in some tissues, so telomerase activators may well do some good.  Probably not as much as a lot of people think, but some.



#6 Logic

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Posted 19 February 2016 - 11:44 PM

Telomeres shorten for other reasons beside cell division.  Primary among these is oxidative damage.  There may be high turnover in the gut, but there is not high turnover in muscle, however telomeres still shorten there.  That might be oxidative damage due to muscular exertion.   Telomerase acts preferentially on critically short telomeres, so if you do manage to induce some telomerase activity, it will probably not do you much good unless you have some short telomeres.  Of course, in an aged individual, there will probably be a non-trivial number of critically short telomeres, at least in some tissues, so telomerase activators may well do some good.  Probably not as much as a lot of people think, but some.

 

Note that the opening post/study proves my point Niner.

"...Short telomeres accumulate in the gut...telomere shortening and DNA damage in key tissues triggers not only local dysfunction but also anticipates the onset of age-associated diseases in other tissues, including cancer."

As for telomerase activators, and anything we eat really, having a better chance of having a greater influence on the cells of the gut than elsewhere; I'm just following my gut.  The deduction seems logical?  :)

I also assumed that the stem and progenitor cells replacing the senescent gut cells are located closeby enough to benefit from oral telomerase activators...

yep:

".,.Recent studies have suggested that ISCs are located either at the crypt base interspersed between the Paneth cells (eg, Lgr-5+ve cells) or at or near position 4 within the intestinal crypt..."

http://www.ncbi.nlm....les/PMC2965634/

 

It seems my logic is imperturbable...this time...  :)

 

 

Everyone:

An informative read:

Oral Absorption, Intestinal Metabolism and Human Oral Bioavailability

http://www.intechope...ioavailability-


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#7 Logic

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Posted 19 May 2016 - 12:45 PM

Further proof that Astragalus is probably mainly fixing the gut and that the decrease in NF-kB is what is having system wide pro telomere effects:

 

...Astragalus IV appears to have an apparent oral bioavailability of 2.2% in rats when serum was measured by HPLC with mass spectrometric detection after solid phase extraction[26] and the one human study to attempt to measure Astragalosides in serum could not find any...

 

http://examine.com/s...s membranaceus/

http://www.ncbi.nlm....pubmed/16507649

 

NB:

  • ...Angelicae Sinensis increases bioavailability of Astragalus flavonoids...
  • ...Astragalus membranaceus and Angelicae Sinensis are highly synergistic, meaning they are more powerful when taken together.
  • This combination is traditionally called Dang-gui buxue tang...
  • ...Astragalus appears to have the ability to inhibit the CYP3A4 enzyme, and may increase the AUC of some pharmaceuticals when coingested...

http://examine.com/s...s membranaceus/


Edited by Logic, 19 May 2016 - 01:04 PM.


#8 SearchHorizon

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Posted 20 May 2016 - 06:23 AM

If you note, in this literature and others, the comments are always "short" telomeres, not ZERO length telomeres.  I'm not a cell biologist, but I think there is sufficient evidence that extending telomere length in *all* the bodies tissues would go a long, long way to elimination much of the decimation to the body that comes with the years.  I don't believe the only thing to telomeres is increasing the Hayflick limit in cell divisions! 

 

I also wonder about the biolavailability of the oral telomerase supplements, and even if it a small amount that survives the digestive process, I wonder their effectiveness in activating telomerase in all the of the tissues necessary for a true "anti aging" benefit.

 

Based on what I read, I think the DNA strands need the telomeres not just for cell division, but for transcription. Without it, its ability to function appears compromised. I'd guess that whatever is encoded on the portions close to the telomere ends probably are first to be compromised, leading to age-related diseases.


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#9 ceridwen

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Posted 20 May 2016 - 08:46 AM

So in order to cure the serious diseases of old age or maybe even aging itself the telomeres need to be replaced.

Edited by ceridwen, 20 May 2016 - 09:29 AM.


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#10 ceridwen

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Posted 20 May 2016 - 09:44 AM

Your hypothesis seems intuitively correct it might actually explain why these diseases and aging itself seem to be incurable. Hopefully people might research this soon as it could be an important piece of the puzzle

#11 Logic

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Posted 20 May 2016 - 12:17 PM

Based on what I read, I think the DNA strands need the telomeres not just for cell division, but for transcription. Without it, its ability to function appears compromised. I'd guess that whatever is encoded on the portions close to the telomere ends probably are first to be compromised, leading to age-related diseases.

 

 

 

I feel that, simply put, long telomeres curl round and affect genes closer to the centre of the DNA strand in a epigenetic way:

 

http://www.longecity...ndpost&p=754819

 

http://www.longecity...man-skin/page-2

 

http://phys.org/news...-landscape.html

 

http://www.longecity...ene-regulation/

 

http://www.longecity...me-alterations/

 

http://www.longecity...-telomere-loss/

 

Also high levels of oxidative stress cause telomerase to migrate to the mitochondria to protect them, so less will be available to lengthen telomeres in the nucleus..?

http://www.longecity...ndpost&p=704371

 

This, and the above, could be the reason, or part thereof, for the rejuvenation seen with C60oo

http://www.longecity...scussion/page-4

 

Personally I saw dramatic effects when combining a telomerase activation stack with C60oo, but I also started Epitalon (also a telomerase activator) at the same time.

I had done the telomerase activation stack before, but without Epitalon and C60oo.


Edited by Logic, 20 May 2016 - 12:21 PM.


#12 Logic

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Posted 20 May 2016 - 12:30 PM

ceridwen:

Not replaced but kept long and even lengthened.
Telomeres are lengthened by Telomerase.
Some cells express quite a lot of telomerase naturally, like stem and progenitor cells and these are the cells that replace the worn out cells in the body.

There is lots of research on telomerase.

Liz Parish of BioViva has even been injected with a modified virus that is designed to add an extra telomerase gene to ones DNA.

If you click on Search in the top menu; a submenu will drop down.
Click GoogleSiteSearch and type in: 

telomeres telomerase

 



#13 SearchHorizon

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Posted 20 May 2016 - 01:35 PM

 

 

I feel that, simply put, long telomeres curl round and affect genes closer to the centre of the DNA strand in a epigenetic way: ...

 

Personally I saw dramatic effects when combining a telomerase activation stack with C60oo, but I also started Epitalon (also a telomerase activator) at the same time.

I had done the telomerase activation stack before, but without Epitalon and C60oo.

 

 

It seems that you are saying that it is not necessarily the ends of DNS strands that are problematic, and that the malfunctioning portions are determined by the geometry of the DNA and telomeres, as well as the context in which biochemical reactions occur, right?

 

As for C60oo, I can't quite understand the mechanism of its action. To me, it makes no sense that it should have a positive effect on cells. If, as someone suggested, that C60oo functions as a carrier, it would make sense to take it with something that nitochondira could use more of, but usually have difficult time getting it inside mitochondira (not just olive oil).

 

.


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#14 Logic

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Posted 20 May 2016 - 03:47 PM

It seems that you are saying that it is not necessarily the ends of DNS strands that are problematic, and that the malfunctioning portions are determined by the geometry of the DNA and telomeres, as well as the context in which biochemical reactions occur, right?
 
As for C60oo, I can't quite understand the mechanism of its action. To me, it makes no sense that it should have a positive effect on cells. If, as someone suggested, that C60oo functions as a carrier, it would make sense to take it with something that nitochondira could use more of, but usually have difficult time getting it inside mitochondira (not just olive oil).


The telomeres ARE the ends of the DNA strand.
They are said to not contain any genetic information and are there to avoid losing genetic information when cells divide. 
When long they interact with the genes elsewhere in the DNA stand.
As they shorten with cell divisions these specific interactions cease,  almost as though they can't reach the genes they should anymore.

The effects similar to epigenetic changes IIRC/IMHO.  

The bottom line is that their length contributes to aging well before we run out of telomeres, so we want to keep them as long as we possibly can.

C60oo:
It could be that the polyphenols in OO are very good for mitochondria, but don't get anywhere near them without the help of C60.
Then again there is evidence that C60 by itself is a free radical 'sponge', so perhaps its the polyphenols getting the C60 to the mitos.
Perhaps the combination is needed to get to the mitos.
No one really knows.

The point I was making is that; if the mitos are protected by whatever means, telomerase will stay in the nucleus were it can keep telomeres long and even lengthen them a little.
If you add telomerase activators; so much the better.
C60oo just looks to be the most economical and accessible way of protecting them atm.

Tiron is very interesting in that it mops up iron freed by sunlight especially, in mitochondria, giving 100% protection against UV light.

This freed up  iron really buggers up mtDNA, so I am surprised by the lack of interest in Tiron.
http://www.longecity...ed-antioxidant/

 



#15 SearchHorizon

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Posted 21 May 2016 - 01:43 AM

Logic,

 

I have been thinking about telomeres reaching toward the center of DNA strand ... but that scenario doesn't seem likely to me. When a person is born, she/he has about 10k base pairs. I believe a DNA strand (not counting telomere) is 3 billion base pairs long. So, there is no way that a telomere could reach the centromere, even if we assume that the telomeres have been unwound, and the rest of DNA remains in packed configuration.

 

It seems to me that the areas of DNAs most affected must be toward the ends, or near telomeres. I could be wrong of course ...



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#16 Logic

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Posted 21 May 2016 - 09:20 AM

Logic,

 

I have been thinking about telomeres reaching toward the center of DNA strand ... but that scenario doesn't seem likely to me. When a person is born, she/he has about 10k base pairs. I believe a DNA strand (not counting telomere) is 3 billion base pairs long. So, there is no way that a telomere could reach the centromere, even if we assume that the telomeres have been unwound, and the rest of DNA remains in packed configuration.

 

It seems to me that the areas of DNAs most affected must be toward the ends, or near telomeres. I could be wrong of course ...

 

No idea atm SearchHorizon.  Its been a while since I scanned the studies/abstracts.
The 'reaching around' is just an easy/simple way to picture it! :)
The research is all linked in post # 11.
One would need to go through it all carefully to get a better idea of exactly how it all works, but work it does!

Enjoy! :)







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