[Johnnyvee]

There is currently an ongoing clinical trial in Colombia conducted by an American company called Libella gene therapeutics, in corporation with Sierra sciences and a few others.
http://www.libellagenetherapeutics.com/
https://www.sierrasci.com/

This trial is by far the most interesting thing to happen not only in the field of biology, but in science as a whole this side of the millennium. (In my opinion.) It`s the culmination of a long list of in vitro studies,(cells in a petri dish) and in vivo studies in mice involving a form of gene therapy called AAV. It basically involves hijacking a benign virus in order to deliver a payload(a gene) into the cells in an effective manner. This technology has only very recently become safe enough for use in human subjects. It is however still very expensive.

The gene delivered here is a gene that allows the cells to express telomerase. Telomerase is an enzyme that repairs the caps(ends) of the chromosomes that get a little bit shorter each time a cell divides.
We start out with about 15k base pairs at the beginning of life. That is reduced to about 10k at birth, and death is associated with about a 5k base pair telomere length. Although there are some conflicting data, the majority of studies(and there as tons) indicate that the chromosomal instability and radical mutations that follow as a consequence of short telomeres are the cause of cancer. But also short telomeres are associated with pretty much everything that is bad health wise. Cells simply can`t function or divide and you see increased apoptosis, reduced viability, cells that go rogue and attack healthy tissues, and as I said cancer.

Although this is contested, you can make a very convincing argument that telomere shortening is the only cause of aging in humans. Everything else follows downstream from short telomeres.
There are many forms of ageing in different organisms, but primates probably age by telomere shortening. We have the gene that expresses telomerase, but it`s repressed by a protein.
https://en.wikipedia.org/wiki/Repressor


Certain natural products (and two pharmaceuticals) can to a small extent lift the repressor and allow for mRNA to read the telomerase gene. Gene therapy allows for full expression.

This repression of telomerase is an evolved trait as ageing would have been an evolutionary advantage at some stage in the history of life. This on order to shuffle the genes faster to adapt better to environmental changes. Out with old, in with the new basically! Not for all species though, as there are quite a few immortal organisms on the planet.(clams, probably lobsters and quite a few plants also.) Also for most of the history of life, immortality was the norm. Cells just divided and multiplied but there was no senescence. This adaptation came in much later, after the dawn of (complex/true) multi-cellularity, about half way through the history of life on the planet. It should also be noted that cancer is just that form of life, it`s the default state of our own cells, the way they existed prior to becoming multicellular. (Before cells talked to each other)
https://en.wikipedia.org/wiki/Cellular_c...munication

Cancer involves the lack of growth control in cells, simply because this was the name of the game of the evolutionary competition between cells at this stage. It was all about growing as much as possible, and there was no need to reign in growth as cells were not part of a larger organism. (just like bacteria today.)
When telomeres get short (and mutations build up), the cells seem to revert to their default state and start this uncontrolled growth pattern again. Hence avoiding cancer is all about keeping your telomeres from getting critically short.
(Also general oxidative damage to the rest of the DNA will contribute towards cancer via mutations again.)
Another way to see it is that curing cancer and curing ageing are one and the same, since cancer mostly is a consequence of ageing cells, i.e. short telomeres. Things like viruses can contribute towards cancer also through increased immune cell proliferation, and the resulting short telomeres. This is probably why you in rare cases see children get cancer, which are usually immune cancers, and not the type of cancers you only see in adults.

Further evidence that telomere shortening is the main cause, (if not the only cause of ageing) is found in organisms that don`t display much, if any senescence. Lobsters are a good example of this. Like all really long lived organisms (certain clams, tortoises etc.) they have both telomerase activated in all cells, and also very powerful endogenous antioxidant mechanisms. https://www.ncbi.nlm.nih.gov/pubmed/9849895
The same is true for certain clams, some of which have been recorded as close to 500 years old. (clams have growth year-rings.) Lobsters keep growing, and only get larger and more fertile as they age. Of course their risk of dying increase with each year they live, as there are may external causes that can kill them, like infections, predators etc. But they do not display any signs of ageing as I said, which is true for clams and some other organisms as well, that all again express telomerase in all cells.



Lobsters get bigger as they age and have been recorded at close to 50 pounds, and estimated to be close to a 150 years old. They display no signs of ageing, but do have problems getting enough energy with their massive size, increasing their the risk of death.

There are some natural products and two synthetic molecules currently available that are small enough to be allowed into the cells without the need for gene therapy. The most potent are; Astragalus, Rhodiola, broccoli seed extract, chia seed extract, vitamin D3, and a few others. (I`m doing a few of these myself.) The most potent are the synthetic TA-64 and more so, something called TAM-818. Both based on the astragalus plant. TAM-818 is orders of magnitude more potent as TA-64, and allows for expression of telomerase at about 16 percent of the limit where your telomeres will actually get longer rather than shorter, and you will then theoretically get younger. (We shall see soon.) The good news is that when the telomerase enzyme is activated to a smaller extent, it seeks out the critically short telomeres, which are the ones that cause trouble as described above. So you will not see any increase in average telomere length with these, but the disease causing critically short ones are elongated and you will also to some extent will slow down the rate of ageing/telomere shortening.

The production of the gene therapy using the test subjects own cells is a very expensive and laborious task, and why the cost of gene therapy is quite astronomical at the moment. But as with most technology, what was in the beginning only available for the wealthy tend to become affordable for most eventually. It takes about 4-12 months to produce the quadrillions of cells that will deliver the telomerase enzyme to all cells in the body, but the first indications of efficacy could be ready around May-June. (But Autumn is more likely.)
The scientists that designed the study have tests in place from day 1, then day 3, 9, 27 etc. (standard procedure) In the mice study done at Harvard a few years back, it took about 3 weeks before the mice showed signs of rejuvenation. This included improved insulin sensitivity, bone density, memory,(maze test)virility returned, hair coat came back dark and dense, energy levels etc. It will be interesting to see if the effect is similar in human subjects. It should be said that mice don`t age by telomere shortening, as they have telomerase. They age by oxidative damage. (As do we to some extent.)They engineer the mice so they don`t express telomerase. However it`s hard to see why this shouldn`t work in humans as well, based on all the studies, including the in vitro studies with human cells I mentioned.

There is also a patient that have tried the gene therapy already. Her name is Liz Parrish. Although one subject is certainly not enough to draw any conclusions, and she only got the therapy a few years back, all tests seem to indicate that it`s working. She`s 46 I think, and in my opinion looks more like 30. Another reason to believe this might work in a larger cohort.

Liz Parrish. Definitely a WBAAAVGTR. (Would Bang After Adeno-Associated Virus Gene Therapy Rejuvenation.)

There will of course be a lot of different opinions when it comes to anti-aging and life extension. I think that being able to stay young for a good while in order to experience the things you want in life is a good thing. So is curing most disease, which follows as a consequence if these types of treatment prove successful. (Although many of these anti-aging people have no understanding of anthropology, and are way to reductionist in their approach. Which means they miss simple clues like, for example, the fact that hunter-gatherers have basically no auto-immune disease. No need for a drug in other words, diet change will do.)

Anyway, I think this could potentially be one of the big stories this year, and I just wanted to give you a heads up. The media is generally clueless when it comes to science, and will not be interested unless it`s sensational news. One would believe that actually turning old people young again would garner some attention, and also a lot of money could potentially be thrown at some of these companies. Having followed the evolution of telomere biology, gene therapy and the people involved for some time, I will be more surprised if this doesn`t work than if it actually does. Needless to say the implications could be huge!