Telomerase Therapies in our Future

Telomere biology has the potential to extend human life span, to dramatically lower rates of the great remaining killer diseases: heart disease, stroke, and Alzheimer’s.  All three diseases increase exponentially with age, and their toll will be slashed as we we learn how to address the body’s aging clocks.

You would think that the 2009 Nobel Prize might have done more to raise the profile of research in telomere biology, but the field remains a specialized backwater of medical research, and few biologists (fewer doctors) take it seriously as a panacea for the diseases of old age.  If the National Institute of Health has money to put into heart disease and cancer and Alzheimer’s and Parkinson’s diseases, there is no better place to invest than in telomere biology.  Research on these diseases commands multi-billion dollar budgets, because they are considered “medicine”, funded by NIH, while telomere biology is considered “science” and is funded by NSF.  The total NSF budget for all cell biology is only $123 million, and the portion devoted to telomere biology is a few million. The private sector is doing a little better – there are several companies selling herbs that stimulate our own bodies to liberate telomerase.  But this is short-sighted venture capital, and what we need is focused research with a ten-year vision.

There is good reason to think that telomere length is a primary aging clock in the human body.  The body knows perfectly well how to lengthen telomeres, but chooses not to.  All we have to do is to signal the body to activate the telomerase genes that are already present in every cell.   Of course, there is no guarantee that this will work, but compared to the sluggish rate of progress on individual diseases, it’s a pretty good bet, and the target is rather simple.  IMHO, it’s worth a crash research effort.

Three objections raised against telomerase research

1.  “Aging is inevitable because Physics tell us that nothing can last forever.”  This statement refers to the Second Law of Thermodynamics, which says that closed systems, evolving in isolation, must become more disordered over time.  But living systems are open, taking in free energy in the form of food or sunlight, dumping their entropy out into the environment.  There is no reason that such systems cannot maintain themselves indefinitely.  Indeed, growth and maturation would not be possible if this law of physics applied to open thermodynamic systems. Since the 19th Century when the laws of thermodynamics were formulated, it has been understood that aging cannot be explained from physics, and therefore commands an explanation from evolution.

2. “Evolution has been working to maximize animal life spans in order to increase fitness.  It is unlikely that any simple adjustment to physiology that humans can discover will do better than evolution has done over millions of years.”  In fact, evolution has not worked to maximize life span, but only to make it sufficient to assure time for reproduction.  Aging is a form of programmed death, on a flexible but finite schedule.  It is fixed in our genes.  There are mechanisms of aging that have been programmed into living things since the first eukaryotic cells.  Telomere attrition has been used to time the life cycle and form a basis for programmed death for at least a billion years.  Many species of protozoans do not express telomerase during mitosis (but only during conjugation), so their telomeres shorten with each reproduction, leading to a limit of a few hundred reproductions per cell line.  This mechanism is the precursor to telomeric aging that exists to the present day in humans and many other higher animals.

3.  “Expressing telomerase will increase the risk of cancer.” There is a great deal of theoretical concern in this direction, which I think is entirely misguided.  It is true that cancer cells express telomerase.  It is not true that expressing telomerase causes a cell to become cancerous.  This relationship is clearly explained by two seasoned experts (Shay and Wright 2011)

In early studies, the only way of increasing telomerase activity in lab animals was to add extra genes for telomerase.  Technology in the early 2000s did not permit a gene to be added at a targeted location, but only inserted randomly into a chromosome.  Tampering with the structure of DNA in this way is known to increase cancer risk no matter what gene is added or subtracted.  In three of these early studies, cancer rates in mice were increased [123].

There are no lab studies to my knowledge in which activating the native telomerase has increased the risk of cancer.  The modern view is that “while telomerase does not drive the oncogenic process, it is permissive and required for the sustain growth of most advanced cancers.”  Recent perspectives from both Harvard lab of de Pinho and the Spanish lab of Blasco focus on the potential for telomerase to decrease cancer risk, and these were the very people who produced the three studies suggesting caution a decade earlier.

And there are many studies showing that (a) telomerase expression does not increase cancer risk in lab animals, and (b) short telomeres are a very strong cancer risk.  I believe that telomerase activators will greatly reduce the cancer rate, first by eliminating cells that are pro-inflammatory and potentially carcinogenic because their telomeres have become short, and second by rejuvenating the immune system, which is our primary defense against cancer.  I published an article on this subject last year.

Why we might expect big life expectancy gains from extending telomeres

This is the affirmative question, then: what makes me think that telomere extension will have such a powerful effect on diverse aspects of aging biology?

A)    Telomere attrition is an ancient mechanism of aging.

Protists were the first eukaryotic cells, and they appeared on earth a billion years ago (they were a leap up in complexity from bacteria, which had been around 3 billion years before).  In protists, DNA is linear and hence there are telomeres and a need for telomerase.  Since protists reproduce by simple cell division, you would not expect that the cells would “age” or even that the concept of aging could have any meaning for their life cycle.  But a protist cell lineage can age, and indeed some do.  This is the oldest known mechanism of aging, and it is implemented through withholding telomerase.

Paramecia are an example.  When paramecia reproduce, their cells simply fission, the DNA replicates, and telomerase is expressed.  Hence, telomeres get shorter with each cell division. Paramecia can conjugate, which is a primitive form of sexual gene exchange.  Two paramecium cells merge, mingle their DNA, and then separate.  It is only in the conjugation process that telomerase is expressed.  Therefore, any cell lineage that does not conjugate will die out after a few hundred generations.  This prevents cell colonies from becoming too homogeneous.  Thus aging is a billion years old, and some of the genetic mechanisms of aging have been conserved and passed on through all the transformations of multicellular life (William R Clark has written two accessible books [12] on this topic.)

B)    Telomeres shorten with age in humans.

This has been known for twenty years.

C)    People with shorter telomeres have a much higher risk of mortality.

This was established by Richard Cawthon (2003) in a paper which took the field by surprise.  Researchers before then had assumed on erroneous theoretical grounds that telomere attrition, which was known to occur, could not have anything to do with human aging.  It was assumed that the number of cell replications, though limited, must be sufficient to last through the longest lifetime that humans normally experience.  After all, if aging were as simple as telomere attrition, then the body could solve the problem merely by expressing telomerase.  This would enhance individual fitness.  Why would not evolution have found such a simple expedient?  (The answer, of course, is that natural selection favors aging, for the sake of the demographic stability – an evolutionary force not recognized by most evolutionary biologists.)  In Cawthon’s study, the top ¼ of 60-year-olds in terms of telomere length had half the overall mortality risk as the bottom ¼.  Cawthon had access to a unique database of 20-year-old blood samples, and to my knowledge his study has not been replicated or refuted these 11 years.

 

D)     People with short telomeres have a higher risk of diseases, especially CVD, after adjusting for age.  The association with cardiovascular disease has been consistent, not just in Cawthon’s original study, but also several other studies [Ref Ref Ref].  There are also associations with dementia [RefRef] and with diabetes [RefRef].

E)    Animals with short telomeres also have a higher risk of mortality, after adjusting for age.

This has been established in several bird species [Ref Ref Ref], and in baboons.  In 2003, it was already known that long-lived species tend to lose telomere length more slowly, and short-lived species lose telomeres more rapidly.

F)    In limited studies with mice, telomerase enhancers have led to rejuvenation.  (Mice are expected to be a much less effective target for this strategy than humans, because to all appearances, aging in humans relies on telomere attrition much more so than in mice.)

The first experiment of this type was done in 2008.  In the Spanish lab of Maria Blasco, Tomas-Loba engineered mice that were both cancer-resistant and contained an extra telomerase gene, expressed in some tissues where, even in mice, it would not normally be found.  Cancer-free mice with the extra telomerase lived 18% longer than cancer-free mice with only the normal gene for telomerase.

But soon it was discovered that all the experimental precautions around cancer may not have been necessary.  The same lab Bernardes de Jesus (2011) reported that they could increase health span in mice with the commercial product called TA-65 (widely rumored to be cycloastragenol) with no increase in the incidence of cancer.  Cycloastragenol is a weak telomerase activator compared to man-made chemicals discovered at Sierra Sciences, and even compared to some other herbal extracts.  Nevertheless, the Blasco lab was able to show that the shortest telomeres in the mice were elongated, and that markers of health including insulin sensitivity were improved by short-term treatment with TA-65.

Blasco’s lab then worked with a more potent (though more dangerous) method of telomerase induction: infection with a retrovirus engineered to introduce telomerase into the nuclear DNA of the infected cell.  “Treatment of 1- and 2-year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging.” (Bernardes  de Jesus, Vera et al. 2012)  The mice lived 13% longer when AAV treatment began at age 2 years, and 24% longer when treatment began at 1 year.  There was no increase in cancer incidence.

The most dramatic example of rejuvenation is from the Harvard laboratory of Robert de Pinho.  Normally, mice (unlike people) express telomerase freely through their lifetimes.  These scientists engineered a mouse without the normal (always on) gene for telomerase, but instead had a telomerase gene that could be turned on and off at will by use of a chemical signal that the experimenters could feed to the mice.  As these mice grew older, they developed multiple, severe symptoms of degeneration in the testes, spleen, intestine, nervous system and elsewhere.  All these symptoms were not just halted but reversed when telomerase was turned on late in the animals’ lives. The effect on the nervous system is particularly interesting because nerve cells last a lifetime and do not depend on continual regeneration from stem cells, the way blood and intestinal and skin cells do.  Nevertheless, these mice with telomerase turned off suffered sensory deficiencies and impaired learning that was reversed when the experimenters administered the chemical signal to turn telomerase back on.

Stanford/Geron research group worked with “skin” grown from human cells in a lab setting.  They found they were able to restore youthful elasticity, softness and texture to the cultured “skin” by infecting the cells with an engineered retrovirus that inserted the gene for telomerase.

G)     In addition to its function in lengthening telomeres, telomerase also acts as a kind of growth hormone.

This fact was suspected as early as the 1990s, and confirmed definitively in a Stanford experiment [RefRefRefRef].  In this experiment, mice were engineered with “denatured” telomerase that lacked the RNA template for creating telomeres.  Still, the telomerase was shown to induce hair growth.  Telomerase has been shown to affect a hormonal signaling pathway called Wnt. Other functions for telomerase are reviewed by Cong and Shay (2008).

H)        In one human case, huge doses of herbal telomerase activators has led to rejuvenation.

I am recently in touch with a physicist from Kansas who has been taking super-high doses of telomerase-activating herbs and supplements for six years and claims to look and feel younger, with improved athletic performance.  He may be an interesting case study.  Jim Green has commented on this blog site.

 The Bottom Line

In my opinion, telomerase activation is a field that offers the most potential for human life extension in the next few years.  This research is languishing for lack of funds, and for lack of attention.

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73 comments on “Telomerase Therapies in our Future

  1. Great article, thanks for putting it here for everyone to read.
    Best,
    James

  2. Thank you for this article. Youhave a wonderful site and I really love your writings.

  3. Bridgett Antion on said:

    Thanks for this great article. I’ve been trying to find information about telomerase and just have to believe that there is something in nature that does not require all this high processing to extract the essence of what we need. I’ve seen supplements claiming that animal glandulars activate this enzyme, certain vitamins will activate it and so forth. Could be something as simple as exercise, fresh air, or even “grounding” to the earth. Whatever it is, it’s probably right under our noses.

  4. Hi there, I discovered your web site via Google while searching for a similar subject, your web site got here up, it seems great. I’ve added to favourites|added to bookmarks.

  5. Chris on said:

    Hi Josh,

    I’ve enjoyed reading your blog and also your essay in “Lynn Margulis – the life and legacy of a scientific rebel”. I have a (genuine) question:

    Why are you (and others) so focussed on prolonging and preserving human life?

    Many thanks

    Chris

    • Thanks, Chris.
      Your question is about fundamental values and not about science.

      On the one hand, human overpopulation has been a bane on the earth’s bounty, disruptive to the ecosystems created over many millions of years. Overpopulation is a result of lowering birth rates chasing lowering death rates, but not quite fast enough…

      On the other hand, our society spends huge sums of money on medical care, and most of this is tending to diseases of old age. If we as a society are already pouring resources into medical research into cancer and heart disease and diabetes, if treatment of these diseases costs us hundreds of billions of dollars a year and a great deal of suffering, then it would seem to be worthwhile to forestall all of these diseases at once with a generalized program of life extension.

      -JJM

      • Patty Cassin on said:

        Awesome truth…but the fact is the big pharmaceutical companies receive big benefits from our illnesses…so sad!!! I want to have a productive life…not one filled with sickness..and also most people enjoy working… this would also help people to work and contribute taxes to a much longer date.

  6. Alessandro on said:

    First of all, my sincere compliments for the blog.

    I am not a life scientist (I am a mathematician), but I have been a bit puzzled by this post.

    Telomerase is highly expressed in many human tumors (that’s why cancer cells are mostly immortal, namely they bypass Hayflick limit). Suppressing telomerase is considered a target for cancer therapy.
    Moreover, while it is true that mice have highly expressed telomerase, it is also true that most of them die of cancer (I think it is the 80% in lab) where telomerase is expressed in somatic cells. This does not happen with larger animals where telomerase is expressed only in the embryo and in some pluripotent cells, but not in somatic cells. So turning off telomerase seems to be a protective mechanism against cancer.
    It seems that the problem is that cancer cells know how to unlock the key.

    • “This does not happen with larger animals where telomerase is expressed only in the embryo and in some pluripotent cells, but not in somatic cells. So turning off telomerase seems to be a protective mechanism against cancer.
      It seems that the problem is that cancer cells know how to unlock the key.”

      Lobsters are said to express telomerase throughout and are said to have low cancer incidence. Regards cancer, it is said there is a telomerase free alternate method of extending telomeres.

      • guestimate on said:

        And lobsters do grow quite large, in fact they never actually stop growing. Native americans and fisherman of the late 19th century reported catching lobsters off NewFoundland coast up to 6 ft. long. Today’s lobsters are mere fingerlings of their great, great grandparents. I mention this to point attention to possible relationship between telomerase and growth hormone.

  7. R Zargle on said:

    Found TA-65 at $2000 a bottle! Seems like only the wealthy will be able to stay young!
    Hopefully a telomerase inducer will be found cheap enough for an old maths teacher like me! I’d love to keep my mind intact for a few more decades.

    • It’s bad, but it’s not that bad. TA-65 costs a few hundred dollars a bottle, not $2000. You can find it on EBay or Amazon Market.

      TA-65 is widely rumored to be cycloastragenol. You can find cycloastragenol from China far cheaper at these same sources.

      Product B is based on different herbs from different sources. On the one hand, it’s stronger than TA-65 in lab tests. On the other hand, there’s actual clinical data for TA-65 showing its effectiveness, and there is none for Product B. Product B is about $75/month.

      The first ingredient in Product B is Silymarin. You can find Silymarin for much less than Product B. Here’s a web page with other ingredients in Product B: http://www.isasource.com/isagenix-product-b.html

      • A big seller of TA65, claims that milk thistle extract which has Silymarin does not activate telomerase. But given that this is a competing product, an independent test and claim would be more reliable than one from entities vested in outcomes.

  8. Alexandra on said:

    Your article was fascinating in an opposing way and your blogs are truly interesting, but I disagree with your premise!

    Isn’t the increase in telomerase, the potential for a longer cell life, and the increase in the number of cell divisions in its life time going to increase the chance for cancer, not provide youth? As the cell division increases, the oppertunity for an error in cell division to occur increases as well and the chance for cancer goes up? Isn’t that what cancer is, an “error” in cell division? If more time is alotted for an error to occur, it most likely will? If you have read, the scientific world has noted that an increase presence of telomerase has occured in many cancer patients and could be used as a future alert for people who might have cancer. Telomerase is the cause, not the solution. The increase in telomerase allows the cancer immortality. Your article, naive, is written on the pretense of a perfect world where if the protein causes immortality in cancerous cell, then it must do the same for healthy ones. The thing is were not in a perfect world and the effects and complications were not considered. Where both of us are standing, cancer by regulation of telomerase and cancer by an over production of telomerase, cancer is still occuring and nothing seemed to happen, except one life was focused on living and the other was focused on prolonging life.

    Sincerely,
    Ali

    • Alexandra –
      You are correct that there is a widespread assumption among biologists that “it can’t be that easy” – that if evolution had such an easy path to a longer life span, then we would have evolved to express telomerase. So the view you express is quite traditional. Judith Campisi has written on this subject.
      However, the actual evidence does not indicate that turning on telomerase increases cancer risk. There have been experiments with mice in which telomerase is turned on, the mouse lives longer, and cancer risk is not increased. Furthermore, people with short telomeres have much higher risk of cancer. I have written a paper on the subject, to be published next month.

      • George on said:

        I may be naïve, but germ cells express telomerase throughout life; yet germ cell cancers are far less common than epithelial cancers, which argues against the correlation between telomerase/tert expression and cancer. Also, I hazard to guess that telomerase activation is not the “cause” for cancer, but it is necessary for cancer cells to turn on telomerase to escape the Hayflicks limit similar to several other pathways that it turns on (or off) to achieve immortality. If the argument is true, then activating telomerase is necessary for cancer cells to achieve immortality, but activation of telomerase may not automatically induce cells to become cancerous. Besides there are many cancers where there is no activation of TERT and uses other mechanism to overcome the Hayflick limit. I would also guess that for those how already have the sub-type of cancers that are more dependent on telomerase activation for survival, activating telomerase by telomerase activators may be bad. In this vein, one has to acknowledge that telomerase inhibition does not kill all cancer cells that have increased telomerase activity. It seems that a lot of things about telomerase is not understood due to the lack of research and the hypothesis that cancer will be automatically induced upon activation of telomerase is more conjecture than based on scientific fact and on experiments where activation of telomerase by recombinant viral vectors carrying copies of TERT increases incidence of cancer in mice, which in itself cannot be extrapolated to increased incidence of cancer in humans upon activation of telomerase by mild activators of telomerase.

        • Steve H on said:

          I agree with Josh Telomerase activation does not cause Cancer, if anything short Telomeres allow Cancer to hijack cells. It has been observed in studies that Telomere length falls until the cell is hijacked then the Telomerase rises again as Cancer takes over. Cancer progression is a multi faceted situation and Telomerase is only one component.

          Also of interest is this new study from CNIO where Blasco et al have managed to effectivly turn cancer off by attacking the Telomeres via a different method and it is looking very promising. This is the same research facility that has made so much progress with Telomerase rejuvenation.

          http://www.eurekalert.org/pub_releases/2015-05/cndi-csa051115.php

  9. I used ta-65 for a little over a year, while deployed in Afghanistan (as a contractor, I could afford it, though only 1/2 dose). It did more for me, particularly mentally, than anything I had ever used. I’ve had lasting effects in the reduction of bad anxiety and depression, not a miracle but definitely noticeable.
    I can’t afford it with a stateside job, but I did try the crack aging cycloastrenegol for about 60 days. It just didn’t seem at all to be the same; especially the deep sleep and active dreaming produced by the ta-65. I’d always feel so extremely rested; I get a similar, though not as pronounced effect by taking n-acetyl-cysteine before bed.
    Other effects, my chest hair (I’m 52 but have little grey hair on my head) turned from grey to a mixture of dark brown and some grey. I’ve been off it for 1.5 years now and the grey is coming back again. :(

    Sure wish I could keep taking the ta-65!!

    • I just started with a product for telemere support , its called tsx and is only$125 a bottle. I am hoping for anxiety relief, If ya want I can give ya the site I get it from

      • I know of no evidence that telomerase expression has an effect on mental state.

        • Brett Mack on said:

          Turns out it may not have been the ta-65. I looked back at my order records from LEF, and sure enough I had been taking methylfolate then. I’ve since found out I have a homozygous a12988c mutation, a couple of others for MTHFR and also MTRR. Taking sufficient methylfolate and Sublingual b12 has been enough to get me off prescription antidepressants. Doesn’t much help the anxiety, but depression feels like a thing of the past now.

    • Subjectively and based mainly upon the effects on my dreaming, CAW Hypersorption cycloastragenol works about as well as TA-65. CrackAging cycloastragenol does not work as well.

      • I know there are people who are sensitive to chemicals even when they have no effect on the CNS, but I’m not one of them. I can’t imagine what it’s like. I’d be interested to see you try a blinded test with a friend giving you different pills at random to see if you really can tell the difference.

  10. Well, I think I’ve put Death In Chains with
    http://www.greenray4ever.com/longevity.html ,
    but it takes quite a while to roll through it, and then you have to start
    all over again, to refresh yourself. Ergo it mirrors the Myth of Sisyphus,
    by Albert Camus, which resembles Albert Caw-“mu”s, which reminds me of
    my work on the gravitational coupling constant mu in classical general
    relativity and in electromagnetic-like gravitation, described at
    http://www.greenray4ever.com/unifiedsummary.html . Furthermore,
    the Myth of Sisyphus seems to roll by each year up on the celestial sphere,
    in the constellations. Each year the rock reaches the perihelion of its orbit
    as Orion chases Perseus-Pleiades-Aries across the sky, but there is a phase
    where the Hero of the Stars seems to fall like Bootes perched on the
    Handle of the Big Dipper back into Summer heat.
    For an extensive list of telomerase activators that are being examined, see
    http://www.greenray4ever.com/lifexnotes3b2.html#TAALPHABETICSELECT .
    I don’t think any more extensive list is available online.

  11. Josh, I might have missed this in the comments, but I’m wondering what avenue you have taken? Do you pay the $100’s or do you take one of the cheaper alternatives and still feel the effects, if that question isn’t too personal? I feel I could benefit but definitely don’t have money to waste.

    • I’m always experimenting as I learn. I’m hesitant to share my own practices until they become more consistent. Lately, I’ve discovered that astragalus root is sold by the pound in Chinese groceries, about 100 times cheaper than the pills. I’ve been taking silymarin and ashwaghanda and horny goat weed rather than Product B, also to save money.

      As for “feeling the effects”, this is not why I’m taking these supplements. I’m hoping that they have their effect in the long run. I hope to slow aging over a period of years and decades. Anything I feel today from taking a pill today is a distraction at best.

  12. Com relação a telomerase e câncer, talvez se possa associar a relação que se fazia equivocadamente ao câncer de próstata e testosterona. Se a testosterona fosse a responsável pelo câncer de próstata, a incidência maior seria na juventude quando a testosterona é mais alta. Ao contrario, o câncer de próstata atinge pessoas mais velhas.

    Google translate from Portuguese:
    With respect to telomerase and cancer, perhaps one can associate the relationship that was mistakenly to prostate cancer and testosterone. If testosterone were responsible for prostate cancer, the incidence was higher in youth when testosterone is highest. Rather, prostate cancer affects older people.

  13. Wow! Brilliant article Josh – can’t thank you enough for putting it all together like this!!

  14. L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts.

    See . . . http://www.ncbi.nlm.nih.gov/pubmed/15474517

  15. Patrick on said:

    I’m grateful for this website Josh, and I am surprised at how little scientific work there is on the “aging problem.”

    I’ve recently started a regimen of NR (4000mg) and astragalus (2500mg) at 42 years old and we’ll see how it goes. I have noticed that since starting the NR that my strength in the gym has noticeably increased. I’m now benching more weight than I was when I stopped weight lifting 10 years ago… No, nothing dramatic like sci-if, but only by a few pounds, but still a noticeable amount to myself.

    I’m also a physicist by degree so I’m watching my own experiment and trying to be objective. I applaud your work here, and will keep reading up on your work here.

  16. Patrick on said:

    Just an update and a correction… I am actually taking 25gr of astragalus, not 2.5gr. I’ve not had any bad side effects since beginning this “experiment”. My strength at the gym has definately and noticeably increased. Again, we’re not talking sci-if. I injured my Achilles’ tendons working on my calves with 160lbs (over extended and stretched) and I thought I was going to be sidelined for months and have to see a doctor. It completely healed up within 3 weeks. Not saying it’s because of the supplements, but typically those injuries take 6 weeks to heal.

    All I can really report is that concurrent with beginning NR I experience some gains at the gym that have since plateaued. I hope the astragalus staves off the effects aging and senescence to keep myself healthy and fit in the very long run.

  17. Patrick on said:

    …oh, and yes, I am taking about 1/2 a bottle a day of NR. The same is true of the astragalus. No negative side effects to report. I’ve also added alt-711 to my list last week at about 50mg in the morning, and at night. Being 42, the idea of preventing stiffness in the heart muscle due to old age before becoming old seems like a no-brainier to me. If only there were something for the AGE accumulation in the skin.

  18. Pingback: V.N. Anisimov: Russian Optomist on Longevity -

  19. Garrett Granger on said:

    Great article! Regarding to your comment on neurons:
    “The effect on the nervous system is particularly interesting because nerve cells last a lifetime and do not depend on continual regeneration from stem cells, the way blood and intestinal and skin cells do. Nevertheless, these mice with telomerase turned off suffered sensory deficiencies and impaired learning that was reversed when the experimenters administered the chemical signal to turn telomerase back on.”

    Nerve cells do regenerate, especially glial cells, which form the supportive infrastructure for neurons, so telomerase effects on the nervous system do make sense:
    http://www.ninds.nih.gov/disorders/brain_basics/ninds_neuron.htm

  20. My understanding of relationship between cancer and telomerase is: Lack of telomeres on chromosomes can lead to cancer by allowing corruption of genetic data at or near those ends; rapid cancer cell reproduction triggers telomerase but it is to late. Teomerase should have been triggered before cancer to stop the corruption befoe it happened. I’m not saying this is the only way cancer starts but could be one of them, that allows genetic corruption.
    I made a comment here after reading the research:
    http://triplehelixblog.com/2012/07/fighting-cancer-by-inhibiting-telomerase/

  21. Alex Duval on said:

    Your expression in this blog is logical therefore I see no reason to discount any of the points you raised indeed I share your views,

    As a simple side note AAV’s(in the experiment discussed they are rAAV-because they are recombinant) used by Blasco in 2012(in the experiment discussed) are naturally a double-stranded DNA virus with very stable behavior in mammalian cell-lines, they insert themselves in only a specific location in chromosome 19 but in the case of rAAV they will be episomal(they do not integrate into the DNA, but can be used to express the gene in them – this IS ideal to prevent any risk of random integration which doesn’t occur normally with AAV’s anyway).
    What can be said about retroviruses(or indeed recombinant retroviral vectors is that they are RNA not DNA and may integrate themselves randomly – this IS NOT ideal and may lead to cancer…

  22. Alan Armstrong on said:

    Any Updates? Especially any more news from (H), the physicist that was taking massive doses of telomerase activators. Do we know what they are and is this person willing to let the rest of us in on it?

  23. Alexandru Dumitru on said:

    If world society manages to educate as big a proportion as possible of the population(and also paradoxically raise the life expectancy) humanity will have actually achieved strict replacement rates as soon as possible, possibly as soon as 2050, beyond that if humanity doesn’t find a way to prolong life expectancy in a dramatic way we will be facing a slow decline in demographics,.. Hans Rosling explains it best, look him up on youtube.

    • Thanks for the reference, Alex. I’m not worried about population decline. If it ever happens, it will be far in the future, and there will be lots of time to plan around it. I am worried about overpopulation, and the strain that humans put on the world’s ecosystems and physical resources.

  24. Hiroyuki Seimiya et al, Telomere length influences cancer cell differentiation, Mol. Cell. Biol. doi:10.11.1128/MCB.00136-13, May 28, 2013

  25. Spot on Josh. Telomere activation therapy (eg Htert) once approved should massively boost lifespan and health. There are a significant number of companies now researching the technology ie, Andrews INC etc…

    Coupled with Senescent cell deletion methods also being developed should boost lifespan a great deal. It will also buy time to develop the other therapies associated with age decline. We live in exciting times.

  26. pedro paguntalan on said:

    I can recommend subscribing to health alert.com, secondopinionnewsletter.com, healthandnutrition.com, alternatives.com by dr. David williams, healthscienceinstitute.com, healthandhealing.comby dr. Julian whittaker, dr. Sears.com, doctorhealthpress.com, dr.mercola.com and toolsforfreedom.com.Also realcures.com by dr. Shallenberger.I look and read books and literatures in all directions and then compare them.

  27. Magda Darling on said:

    Good Evening,

    Josh, thank you so much for what you do. This article was so insightful and helpful to people like us……Progressives and of like minds. I/we appreciate what you do. :-)

  28. Adrian Crisan on said:

    A new very interesting + promising study published by professor Helen Blau @ Stanford:

    http://med.stanford.edu/news/all-news/2015/01/telomere-extension-turns-back-aging-clock-in-cultured-cells.html

  29. Steve H on said:

    Yes this is very promising on top of the work by M.Blasco, I am convinced that restoration of Telomere length would be a considerable boost to the body in restoring itself to a younger state.

  30. Scott Brown on said:

    Josh,
    Any thoughts on the announcement of approach to lengthening Telomeres using a modified RNA that encodes a telomere-extending protein? Even avoids the immune response!

  31. Alexandru Dumitru on said:

    In vivo to a human, may mean either specific tissue targeted for delivery of TERT mRNA, or whole body – but given current technical progress or forseable that would be prohibitively expensive probably in the tens of millions$ figure for 1000 bp telomere elongation.

  32. Adrian Crisan on said:

    Have anybody looked into Low Level Laser therapy to induce telomerase?

    I found couple things on the internet:

    “He:Ne laser irradiation induced survival and cell cycle progression effects on human circulating mononuclear cells in vitro”

    http://www.acgssr.org/BioTechnology/V112July2008/Full_Paper/020.pdf

    and another similar paper:

    “Human Telomerase Reverse Transcriptase (hTERT) Gene Expression in Rheumatoid
    Arthritis (RA) Patients after Usage of Low Level Laser Therapy (LLLT)”

    http://ajbasweb.com/old/ajbas/2011/October-2011/1-8.pdf

    These studies I believe, shows that there is a path to activate telomerase via Low Level Laser stimulation, technology that is actually within our grasp. So create a device that does that, doesn’t require huge financial investment. I’m wondering if Michael Fossel, Bill Andrews, etc. have tried this?

  33. Alexandru Dumitru on said:

    Salve Adrian Crisan,

    Hello Adrian nice to see other Romanians interested in this, I am currently trying to develop a relatively cheap way to make a viral vector to deliver the TERT transgene directly to a human cell. I am aware that Michael Fossel is currently trying to develop a repeatable and relatively cheap way to deliver transgene TERT to the human cell using a non-viral liposome(basically fat bubbles that can inglobate DNA withing them) method. He should soon be having results soon. I have never heard of this method that you speak about: TERT(the catalytic component of telomerase) through lasers, please tell us more.

    Salut si numai bine.

    • Adrian Crisan on said:

      @Alexandru Dumitru – very nice that other Romanians are helping by doing research in this field of longevity/reverse aging. Unfortunately, I’m not a “professional” in the field, I’m just an enthusiast, so I cannot tell much more. I do have a background in physics though, and that connection between lasers and telomerase activation caught my eye. I’m researching this on my spare time – which you can approximate how much I have, by how long took me to post back here on Josh’s blog … – so I cannot add much more to what I have read in these articles. However, I think would be interesting (re)searching this path for telomerase activation, since it goes hand in hand with nano-technologies. I have a feeling that far infrared light, also could play a role into this. I do believe that nano-technologies implementation into biology of (reverse) aging will play a huge role, and as of now, we just see the tip of the iceberg. For example see Google’s patent for Nanoparticle Phoresis:
      https://patentscope.wipo.int/search/en/detail.jsf?docId=US130905048&recNum=13&maxRec=14852&office=&prevFilter=&sortOption=Pub+Date+Desc&queryString=PA%3AGoogle+&tab=NationalBiblio
      From a simple physics stand point, we know that energy can be transformed in mass and vice-versa, so in theory any (adequate) energy stimulation at a cellular level, can lead to interesting and promising results. Somehow, could be a lot easier to yield some results this way, than the other mentioned paths.
      Anyway, meanwhile Josh published some very interesting news about Michael Fossel’s activity with newly formed BioViva. Let’s hope that the results with their work will be as most of us hope: great.
      BTW: do you do your research across the ocean in EU or here in US? Does your research group have a web site we can look at? or a LinkedIn profile?
      Numai bine! All the best!

  34. Chris Lewis on said:

    Josh,

    I’m really enjoying your site. I noticed your mention of the fact that cycloastragenol is a relatively weak telomerase activator compared with some other man made chemicals and herbal extracts. Could you please tell me where I might find more information on these other substances, especially the herbal extracts, particularly how they relate to cycloastragenol as telomerase activators?
    Thank you very much in advance.

    • This is not published information. I heard it from Sierra Sciences, which does the telomerase-activation assays for several of the companies that sell these products. They say the best is TAM-818, which was actually developed at Sierra, now marketed by OneTruth, New Zealand, but only as a skin cream.

  35. frank6 on said:

    I tend to disagree with one of the previous correspondent’s assertion that the delivery of hTERT into cells in the body would be extremely expensive.
    Perhaps I could refer all to the Blasco et al patent (Telomerase reverse transcriptase for protection against ageing – EP 2402038 A1).

    When one sums the actual cost of the materials used they come to far less than a year’s salary. The catches of course are many in number. One needs primarily to understand the language and terminology used (molecular biology), the relative safety of the procedure as related to the relative safety of various alternatives, the efficacy of the procedure, and then take an estimate on the unknowns. Many of these issues are already covered in the patent (for that particular procedure).

    I am not suggesting replicating the patent and selling the result but what I am saying is that there is a whole raft of information there in educating one about the procedure.

    Further, this happens to be the age of the “Wet Garage”. I will leave that one for the site to ponder.

    In my opinion, what is needed is a dedicated few (apparently there are some corresponding on this site) to begin/continue some “wet work” in order to push the “peoples’ solution” to this aging problem to a conclusion, as those writers and thinkers before us have already pioneered (Blackburn, de Grey, Blasco, Jaskelioff, Blau, et al). T’would be quite a coup.

    I have read extensively on this subject including the cancer risk associated with telomere lengthening. The area is vastly written about in various scientific journals. Let me know if you require specific enlightenment. I may be able to assist.

    frank6

    • Thanks for your interesting thoughts, Frank.

      I know of someone who has put together a credible team to do hTERT gene therapy abroad, looking for patients/subjects at a few hundred thousand dollars per treatment.

      And I would like to learn from your readings on telomerase and cancer. I am writing about that subject, and would like to ask for the strongest lab evidence you have encountered suggesting that telomerase might increase cancer risk. (My belief is that extending telomeres is likely to decrease cancer risk. http://link.springer.com/article/10.1134/S0006297913090125

      – Josh

      • frank6 on said:

        Hi Josh,

        I have given some thought to your request and cannot recall lab evidence, or envisage the likelihood, that telomerase would increase cancer risk or increase cancer occurrence. It sounds a little like the impossibility of proving a negative. One never knows.

        There are perhaps exceptions which I could envisage one of which could be an appearance of precancerous cells which have not yet learned how to harness telomerase production. But even then it would be a currently indeterminate matter whether the extended telomeres would silence the (or one) cancer promoting active gene in the particular DNA string. Perhaps a very small chance of cancer. But even then there are so many cancer solutions appearing (in R&D of course) that most of those cells could be picked up in tests.

        Another exception may be a cancer with a preponderance of double strand breaks. Who knows just what telomerase (or any other enzyme) would be doing in those extraordinarily complex situations.

        And another instance would be that which would happen in germ and stem cells which appear to have their own adequate supply of telomerase. What happens if a greater amount is supplied?

        And all of the above does not exclude the unknown reactions (and possible molecular biological necessity) of (naturally) having and using telomerase for other purposes in the cell.

        Proceeding along the lines of the preponderance of lab studies which indicate startlingly positive outcomes for telomerase use in somatic cells and the perhaps almost zero evidence for the opposite, one would presently feel quite justified in using telomerase for improved health.

        But there again, as I have mentioned previously it appears to be a simple matter of risk/benefit analysis. I feel that such a risk/benefit approach in the Western world is not in vogue at this time. I won’t go into the reasons, real or suspected, for such a state of affairs. Nevertheless it seems to be quite a valid approach and a possible set of criteria to many human situations.

        So perhaps you are suggesting an avenue for justification of pursuing such a promising therapy (such as telomeric therapy) which simply cannot be totally (100%) vindicated at the current level of technology. One could probably feel that there might be dozens of hazardous outcomes including cancer for a cell with this type of intervention, but it seems that all of them could be minor and eliminated by the cell itself on early recognition.

        This does not answer your implied question as there is no answer. However I hope that such an opinion might assist in seeing that there is probably a better method of analysis for the therapy’s envisaged future (current?) use.

        Regards,
        frank6

        • Frank – I think it’s simpler than this. There are experimental results indicating that telomerase therapies will DECREASE risk of cancer. What we observe is the difference between known mechanisms that facilitate cancer, and larger known mechanisms that prevent cancer.
          – Josh

    • Alexandru Dumitru on said:

      Dear frank6,

      I did not obtain the explicit approval of the authors of the patent Blasco et al patent (Telomerase reverse transcriptase for protection against ageing – EP 2402038 A1), so I cannot post the figure which shows the method used in the patent(a well known but far from cheap or cost-effective in any way) to deliver the hTERT gene. The figure is titled figure 1A and 1B at Arama Raporu (5) – the fifth picture from left to right. The method discussed in the patent you mentioned is also called tri-plasmid rAAV(AAV=adeno-associated virus) method and it is best explained at this site:

      http://www.genetherapynet.com/viral-vector/adeno-associated-viruses.html

      The product of the patent you mentioned was used in the article:
      Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer – Bruno Bernardes de Jesus, Elsa Vera, Kerstin Schneeberger, Agueda M. Tejera, Eduard Ayuso, Fatima Bosch, Maria A. Blasco.

      The method is far from cheap because for even a small number of viral genomes(carrying the transgene – in this case hTERT) three different sets of plasmids need to be generated through the usual molecular biology methods and then purified…

  36. Alexandru Dumitru on said:

    I am currently working on my Master’s thesis ( at Bucharest University) which will explore the way in which the TERT gene(the molecular machine may be delivered using adeno-associated virus(AAV for short). TERT actually does the extending of telomeres using TERC RNA component – a sort of “matrix” if you see what it spells out it spells out 5′-TTAGGG-3′ in reverse and in RNA (of course) so it would be 5′-CCCUAA-3′ ). But it appears that the TERT component is what is missing in adult somatic cells, where telomere extension does not take place.
    In the near future I plan to pursue this venture , perhaps in the US with Michael Fossel.

  37. frank6 on said:

    Thank you Josh for the reassurance on the telomere lengthening question. Nice to get input from a professional source.
    Perhaps you could help me with something that’s been on my mind for quite a while and that is the very large differences in rejuvenation results of Jaskelioff and Blasco on mice. They both use essentially the same method ie. adding telomeres to the chromosomes for rejuvenation.
    What is the reason for this large discrepancy?
    frank6

  38. A potential immortal on said:

    Your statement about entropy and life is unfortunately, or fortunately wrong.

    Entropy of Life can be considered as decreasing since it is not a closed system.
    en.m.wikipedia.org/wiki/Entropy_and_life

    • I think we have no disagreement.
      When I look at what I said, it seems clear to me, and consistent with what you are saying.
      Living systems are able to reduce their internal entropy by increasing the entropy of their environment. That is the essence of not being a closed system.
      Where is the misunderstanding?

  39. Vikas Saini on said:

    “there has been one heart patient who has received the AAV/myostatin treatment it with excellent results. ”

    reference?

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