Telomere & Telomerase: In age preventive treatments

Telomere & Telomerase

in age preventive treatments

There are many pills and drinks containing natural compounds claiming to have age preventing effects. One of the many things it targets is telomeres, helping telomere regions to stay healthy and at full lenght. Is this possible thou? or is it simply another way for companies to steal some money? We shall take a look at how it works and if there are any scientific progress supporting these claims. I´ll try to keep it as short as possible, enjoy.

introduction

The word Telomere comes from the greek words telos and meros, meaning end-part. This is exactly what it is, the end part of our chromosomes. The telomere region is characterized by being a repeat of the sequence TTAGGG, which describes the nucleotides it is made up of, Thymine,Adenine,Guanine in the given sequence.

This sequence is repeated about 2,500 times, making up the Telomere region and its purpose is to protect the chromosomes from degrading during replication of DNA. At birth we have 11 kD, the weight of the telomere region in kilo Dalton, but at age 80 it seem to be around 4 kD heavy, linking it to aging.
This has spawned a lot of debates whether it could be targeted for age preventing treatments and this post will present the mechanism behind creating the telomere as well as look at the success of prior ideas of treatment.

Functions and structure

First of all During DNA replication, the DNA strand is cleaved into strands and synthesized into two new strands. The replication of one of the strands, called the lagging strand, or 3´strand, is dependent is fragments called Okazaki Fragments which are placed after the replication fork then synthesized backwards. DNA polymerase needs this fragment in order to bind and replicate the DNA since it cannot bind directly to single stranded DNA.

At the tail of the lagging strand the fragment will have no place to attach to.The other strand will have a telomere repeat at the end, so that it will be targeted by telomerase and receive an alternative okazaki fragment and be fully replicated. Telomerase is the Enzyme that is responsible for synthesizing the alternative binding site for DNA polymerase as well as elongating the TTAGGG repeats protecting the ends of the chromosomes. Telomerase is a TERT, telomerase reverse transcriptase. If you find this hard to grasp i recommend looking at an animation of DNA replication or reading my post on a simplified replication procedure called PCR.

My post o PCR
Animation of DNA-replicaiton




So why is this procedure altered with age and could it be targeted to prevent aging or is the side effects to severe if this is even possible? To address this a few important points must be investigated:

• If telomerase decay was prevented, would it even lead to cell survival?
• Has previous ideas & trails yielded any success?
• Do we even know enough to target telomeres medicinally?
• Does natural treatments show any effect? and what do they state to target?
  
  
  
  

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To some research!

First of all there are many studies that have been conducted on the effects of telomere shortening and its effects on biological processes.

But most of them seems to focus on diseases related to certain changes in telomere length, this points to a situation where telomere altering is dangerous and maybe not suitable for a medical target.
On a human level, there has off course not been any trails, this would be dangerous, especially with genetic approaches.

The few genes we have studied and manipulated in order to receive longer or shorter telomeres are yielding unclear results, both lengthening and shortening at different regions.

In 2015 we got some promising news from Stanford, were they have seen up to 40 times more cell divisions than untreated control cells.

https://biox.stanford.edu/highlight/telomere-extension-turns-back-aging-clock-cultured-human-cells

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The procedure, which involves the use of a modified type of RNA, will improve the ability of researchers to generate large numbers of cells for study or drug development, the scientists say. Skin cells with telomeres lengthened by the procedure were able to divide up to 40 more times than untreated cells. The research may point to new ways to treat diseases caused by shortened telomeres.

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From the article:Telomere extension turns back aging clock in cultured human cells

This is done in skin cells alone and they the only assay used is for telomere lenght, confirming that indeed changed lengths was really the cause.

The team used modified RNA containing the sequence for TERT, an active component of the enzyme we talked about, Telomerase. This makes it possible for transcription to hang on slightly longer and extend the telomere region
I sadly suspect that this will have wide and sever side effects, cells do not divide infinitely for a reason.

I also suspect that these skin cells would be in terrible shape if we used other assays, e.g for cancer scanning. Any treatment based on this premises would have to be done on a genetic level placing it long away in the future, if it's even possible. Only more data and computational power can answer this.
Supporting this claim is the silence since 2015, the same old work has been published again during 2017 but nothing new at on the horizon.

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In 2017 an interesting study published correlations between telomere length and extinction risks in lizard populations.

https://www.nature.com/articles/s41598-017-17323-z

The study spanned from 2005 to 2017 and focused on global climate changes and more specific, temperature.

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Telomere length (TL) analysis represents a promising molecular tool with which to raise the alarm regarding early population decline, since telomere attrition is associated with aging processes and accelerates after a recurrent exposure to environmental stressors.

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Herer we can see the reported correlation between telomere length and extinction composite score.

They found clear correlations between shortening of telomeres and extinction risk. The data speaks for itself and it seems clear on both a cellular level and in larger organisms that telomere shortening promotes cellular death.

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It has been known a while that Proteins p80 & p95 are involved in regulating telomere length but not necessary for telomere regions to form.

Study on the proteins p80 & p95

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Here, we test the functions of p80/p95 in vivo. Surprisingly, telomerase RNA accumulation and telomerase activity in cell extract are unaffected by loss of the genes encoding p80/p95. However, in the absence of p80/p95, telomeres become elongated in both macronuclei and micronuclei
When it comes to finding diseases related to either to long or to short telomeres, information is more abundant.”

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Perhaps the expressed levels of p80 and p95 could be targeted at a post transcriptional, pre translational stage, and leave out the need of direct genetic methods. It would be easier to lower the concentrations thou, compared to increasing them without directly injecting them. In theory and probably practically, I would be able to grow these proteins in my home and inject myself, just saying :) it's not that hard in 2017.

http://www.bsrlabs.com/contract-cell-culture

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Another known factor is the TRF1 telomere gene.

This gene is a part of shelterin, and as u might hear, it shelters telomere regions. Preformed gene therapy on mice using this gene seems to promote life span.

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Interestingly, although AAV9‐TRF1 treatment did not significantly affect median telomere length, we found a lower abundance of short telomeres and of telomere‐associated DNA damage in some tissues. Together, these findings suggest that rescuing naturally decreased TRF1 levels during mouse aging using AAV9‐TRF1 gene therapy results in an improved mouse healthspan.

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Article on TRF1 & aging cells
I've focused my research on credible publications sources, as nature magazine, and newer articles, mostly material from 2017.

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Conclusion

It seems that science have a bit left to sort out and lots of research to do before we will see age medicines based on controlling and maintaining telomere length. I would say 5 years is to short to even sort out a good plan and then 5 years of trailing prior completion, placing any possibilities of a complete product 10 years or more in the future!
There have been a couple of mutations found in telomerase leading to different diseases, but most likely it seems that cancer is.

With targeted gene therapy at young age, this could be targeted with today's knowledge. Sadly for a easier treatment we need to cut and paste the genome with e.g Cas9. Although already showing promising results against inherited cancer, i would guess that 10 years is a good estimate for minimal time before treatments become available.

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Natural products and treatments

Now to the natural products, if you are no fan of waiting 10 years for treatments. To start out i´ve found a rather large report on telomerase activating as health maintenance, controlled by a particular substance,TA-65, in human cell culture. The PattonProtocol-1 delivers capsules to patients containing max 10-mg of active TA-65.

Web site for: The Patton Protocol

Dr. Ed Park was the first outside MD to be licensed to prescribe TA-65 and has the greatest clinical expertise in this field. The cost for the Patton Protocol has been dramatically reduced in the recent years from $25,000 a year to as low as $2,400 a year.
Our patients are seeing amazing results and there have been no side effects.”

There is not much information on the patients when it comes to medical data so it's hard to assess the effect it really has on aging, stem cells and telomere regions.

Article “A Natural Product Telomerase Activator As Part of a Health Maintenance Program”

“TA-65®, exclusively licensed to TA Sciences from Geron Corporation, is a >95% pure single chemical entity isolated from a proprietary extract of the dried root of Astragalus membranaceus and formulated into 5- to 10-mg capsules with inert excipients”

One proposed mechanism for telomere preservation via TA-65 is the changed levels of specific for CD8+CD28− T, which is associated with positive remodelling of the immune system. This will decrease the CD28 content and the CD8+ to CD8- ratio, helping with apoptosis resistance.

Telomere shortening associated with replicative senescence is the probable cause of loss of CD28 expression and apoptosis resistance of CD8+ T cells.54 The decrease in the percentage of short telomeres we found makes upregulation of telomerase by TA-65 the most likely mechanism for this salutary effect.

The study reached inconclusive results according to me and only saw telomere length increase in under 40% of the cell cultures. But as quoted patients show no side effects so why no keep trying it.

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Next up, a serie of products i´ve picked out

The first based on TA-65, TS-X by the companie Sisel Sisel web site

Web page for product

We just read in the section about TA-65, that this could actually work via e.g apoptosis resistance, meaning resistance vs cellular death. It has shown somewhat inconclusive results on cell culture but no reported side effects on humans. Over a longer time span, as dietary supplement the odds of effect would be much greater. I am of the opinion that this could work, I have at least reached the conclusion that this is safe to use!

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The next one is also a product vs aging sold by Sisel, they seem to like anti aging products the most.

Web page for products

This is based on the general idea of unsaturated fatty acids and co-q10, which i would say is healthy to have in a diet, and as a vegan, optional sources like these might be good, even if it's not a problem with proper diet. Nothing more needs to be said, but this is not linked to telomeres sorry. They got another product vs aging but that as well have nothing to do with telomeres even if its healthy supplements.

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At last i decided to check this product out: IsaGenesis, stating to promote telomere health.

Web site for IsaGenesis

After some research all i could find is that the formula contains 30 active antioxidant and as they call it “biotics”. I fail to see how this product in anyway would be linked to telomere preservation. I would opt for berries, seaweed and some herbs, i mean i couldn't even find which 30 ingredients they add.

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Conclusions

I could imagine myself taking TS-X from Sisel, since TA-65 seems safe and also could have positive effects according to multiple studies and the The PattonProtocol. No side effects reported and the links between aging and telomere structure is undeniable.
If you are trying to live longer, stop eating meat and pesticides, this will have a great health impact on must humans.
After that, there are off course dietary supplements that work, just gotta find em!

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Figure 2 wikipedia - Telomerase
Figure 1 & 3 From an religious, Islamic perspective on Telomere, Cancer and aging

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Stay Vegan, Stay organic, Stay healthy!

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Thanks for checking my work out, and hopefully it brought you some insight into the telomere function and where we stand scientifically as well as alternatively on treatments.

I am shockingly positive to the first product i researched, TS-X, and thanks to @BrotherDave for introducing me to it!

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