The Latest from Telomerase Gene Therapy Research

Telomeres are caps of repeated DNA sequences at the end of chromosomes. A little telomere length is lost every time a cell divides and its DNA is replicated, and this is one portion of the limiting mechanism that causes the somatic cells that make up the overwhelming majority of tissues to divide only a set number of times and then destroy themselves. Stem cells on the other hand make use of the enzyme telomerase to add repeated DNA sections to the ends of their telomeres as needed. They must maintain lengthy telomeres as it is their job is to continually spin off new long-telomere somatic cells to keep tissues running smoothly. This is a considerable simplification of the actual situation, but it is good enough for this discussion. The important point here is that if you measure average telomere length in a given tissue, and immune cells from blood are the most commonly used for this purpose at the moment, what you are in fact measuring is a some combination of present cell replication rates, cell replenishment rates, and telomerase activity.

There is a statistically significant correlation between average telomere lengths in immune cells and age and illness across a population. This isn't so useful for any given individual looking at a number and trying to figure out whether or not it means anything for future health, but it is true that the older and more ill a person is, the more likely it is for average telomere length in immune cells to be comparatively short. Is this meaningful to efforts to extend life? That is a question worth asking twice, given that telomere length measures look very much like a secondary marker resulting from the characteristic decline of stem cell activity and tissue maintenance with advancing age, and we really want to aim at primary causes rather then secondary and later mechanisms.

Nonetheless, a fair number of researchers are interested in trying to lengthen telomeres as a potential way to treat illness or lengthen life, and in recent years one research group has used gene therapy to raise levels of telomerase in mice. This turns out to extend mouse life span, with the caveats that (a) short-lived mammals like mice actually have quite different telomere dynamics from long-lived mammals such as we humans, so it is far from clear as to what the same thing would do in people, and (b) it is by no means certain what exactly is going on under the hood here. Is telomerase keeping somatic cells alive for longer, it is increasing stem cell activity, is it perhaps interacting with mitochondria in some way to reduce their contribution to aging, or is some other as yet undiscovered mechanism is at work?

Researchers will come to a conclusion at some point, as there seems to be slow but steady progress towards further investigations of telomerase gene therapy in mice. The same group that pioneered this approach is now heading down the traditional path of attempts to apply this treatment as a late stage intervention for age-related disease and dysfunction. They do this because it is still the only practical way to bring treatments to the clinic these days: approaches are inevitably sidelined into marginal applications intended to be applied after the damage is done. It is a ridiculous situation, and one that causes immense damage to the pace of progress by diverting researchers away from producing methods of prevention.

CNIO researchers treat heart attacks with new gene therapy based on telomerase enzyme

The enzyme telomerase repairs cell damage produced by ageing, and has been used successfully in therapies to lengthen the life of mice. Now it has been observed that it could also be used to cure illnesses related to the ageing process. Researchers at the Spanish National Cancer Research Centre (CNIO) have for the first time treated myocardial infarction with telomerase by designing a very innovative strategy: a gene therapy that reactivates the telomerase gene only in the heart of adult mice, thus increasing survival rates in those animals by 17% following a heart attack.

"We have discovered that following a myocardial infarction, hearts that express telomerase show less heart dilatation, better ventricular function and smaller scars from the heart attack; these cardiac events are associated with an increased survival of 17% compared to control animals." Furthermore, everything points to cardiomyocytes - the cells responsible for heart beating - being regenerated in those hearts with telomerase, a long searched-for goal in post-heart-attack therapy. The regeneration of heart muscle would counter the formation of scars as a consequence of the heart attack, a tough tissue that hinders cardiac function and increases the likelihood of heart failure.

Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction

Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (​Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific ​Tert expression. We find that upon MI, hearts expressing ​Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI.
Comments

I donated another $100 US to the end of year fundraiser (now that my year is about to end). Did we reach our $10,000 goal yet?

Posted by: Carl at December 31st, 2014 5:39 AM

@Carl: As of the morning of the 31st, looks like the total is $8,127.

Posted by: Reason at December 31st, 2014 7:26 AM

Let's hope they will move fast(er) and prove or not, that this path works for rejuvenation. That will help clarify (some) things in reverse aging world.

I watched recently Carol Greider's presentation "How Can Telomeres Cause Age Related Disease".

https://www.youtube.com/watch?v=leW_OY5_Ei4

Posted by: Adrian Crisan at January 1st, 2015 5:36 PM

telomere research must be performed in humans not in rats: it is diferrent in rats.Excessive cell division must be avoided as it would beocme immortal or cancerous. Just ten years would be enough. A 90-year iold coule live for 100 yeara. Sam

Posted by: Kulanayagam at September 17th, 2015 3:44 AM

How many years will it take for science to rejuvenate our telomeres in our cells to achieve eternal youth? DeGray says if enough people give billions of dollars too San, they can do it in 25 years. What is the latest scientific breakthroughs in telomere research; and has anybody,found a way to stop the aging process yet with telomeres? If so please tell me how to contact them.

Posted by: Lee Silber at April 11th, 2018 4:32 PM

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