Life counters
Life and death at the tip of the chromosome
September 15, 2015 healthy forty-four-year-old American Elizabeth Parrish became the first "GM woman": in a medical clinic in Bogota, she was subjected to a procedure prohibited in the United States. She received more than a hundred injections of two experimental genetically engineered drugs designed to reverse the processes of cellular aging in her body. So the former housewife, who by that time had founded a small biotech startup, became, in her words, the "zero patient" of gene therapy for the most insidious and inevitable disease for all people – old age
Before the risky experiment on herself, which she hid even from her family, Liz Parrish was an ordinary mom who took care of the house and helped her husband in the family business. Everything changed in January 2013 when she found out that her nine-year-old son had type 1 diabetes. The disease was formidable, but manageable, but at the Seattle Children's Hospital she saw hundreds of children with the most serious diseases – cancer, heart disease, brain damage, many of whom modern medicine, despite all its power, could not help anything.
Shocked by what she saw, Liz began to look for promising new drugs and medical developments that could radically change the situation. Attending medical conferences, she stopped researchers and experts in the corridors with the question: "How can your work help children?". At one of these meetings, she heard about telomeres – tiny sections of DNA at the ends of chromosomes that play the role of the internal "molecular clock" of the body. And here, thanks to people who were looking for a cure for old age, Liz finally got an answer to her question - after all, healing from death itself should help everyone.
That same fall, she met with a leading telomere specialist, a well-known microbiologist and geneticist Bill Andrews, and the result of this meeting was the creation of the company BioViva with the aim of using breakthrough scientific discoveries to rejuvenate the whole body at the cellular level.
So what was injected into Elizabeth Parrish's body in September 2015 and for what purpose? These were two genetically engineered designs created in BioViva based on a weakened adenoassociated virus. A gene encoding an inhibitor of myostatin, a protein that causes muscle atrophy characteristic of the elderly, was embedded in one of them. The second is a gene encoding telomerase, an enzyme that "sews" new nucleotides to telomeres.
Telomerase contains a short RNA molecule complementary to the telomere region. When binding to the telomere, this RNA is used as a matrix for the sequential synthesis of the chain of the entire telomeric DNA. The second DNA chain is completed during the next cell division.
Telomeres, consisting of identical repetitive nucleotide repeats, in fact, play the role of "protective caps", preventing chromosomes from connecting to each other. With repeated cell divisions, chromosomes lose their "tips" as a result of incomplete copying in the process of DNA doubling, and telomeres are shortened. This process accompanies the aging of the cell, whose life, like the telomeres themselves, ends after 50 cell cycles (the Hayflick limit). The only exceptions are stem cells and, alas, cancer cells: they do not age and are able to divide almost indefinitely, while the length of their telomeres, as in germ cells, is supported by the active work of the telomerase enzyme. In other cells, the gene encoding this protein is usually "turned off".
Progressive shortening of telomeres increases the risk of cancer, as well as the likelihood of developing cardiovascular diseases, type 2 diabetes, chronic obstructive pulmonary disease and some forms of dementia.
With the help of viral vectors that can be embedded in any cell, many "working" copies of the telomerase gene were introduced into Liz's body. Three years after the experiment, it turned out that the length of her telomeres increased, and judging by this length, the cells became almost 30 years younger! This is especially important because the examination before the experiment showed that Elizabeth Parrish has abnormally short telomeres corresponding to the age of sixty, and not the age of a woman of 44. As for the effect of the other drug, it also proved to be effective: Liz's muscle mass increased, and intramuscular fat decreased. Now she feels energetic and healthy, and she has not shown any signs of cancer, which, as feared, could trigger the activation of telomerase.
As you know, in humans, the length of telomeres at birth is 15-20 thousand pairs of nucleotides, and by the end of life it is reduced threefold. However, we must take into account that we are talking about average indicators, and they are measured in humans only for white blood cells (leukocytes). By the way, other organisms living on our planet now and then present scientists with "telomeric" surprises. Therefore, despite the huge experimental material on this topic, there are still fewer answers than questions.
What do we know and what don't we know about telomeres?
Telomeres are the end regions of chromosomes that play the role of "protective caps". A wide interest in them is caused by the emergence of the theory that cellular aging is a consequence of the shortening of telomeres with age
Do identical twins have the same telomeres?
The size of telomeres may differ on different arms of the same chromosome, in different cells, tissues and organs, in twins, in different individuals, in different species. It is still unclear what this variability is related to and what its functional significance is.
Who has longer telomeres – a mouse or an elephant?
In an elephant, it is only 14 thousand pairs of nucleotides, and in some lines of laboratory mice it is 10 times more. It is believed that this is due to the mechanism of protection against cancer available in large organisms.
The older – the shorter? Or not?
The dependence of telomere size on age is not universal: in different organisms (and sometimes in the same organism), their length may decrease or grow over time, and in many there is no such dependence at all.
Is the enzyme telomerase a protein?
Telomerase is a beautiful example of a complex of protein and RNA – a relative of DNA, an "ancient" molecule that performs a variety of functions in the cell. In our case, the protein plays the role of an enzyme, and the RNA serves as a matrix for the assembly of the telomere.
Is it not only age to blame?
Defects in two human genes (SETX and ATM) lead to the development of neurodegenerative diseases associated with accelerated telomere shortening. It is these genes that encode proteins that maintain telomere length in long-lived bats.
Sex or life?
Oxidative stress and hunger experienced by males of the garter snake during the mating season damages DNA, and the energy that could be spent on its "repair" is spent on hunting for the female. Therefore, they live less than females and age faster.
If you want to live a long time, meditate!
According to geneticist E. Blackburn, who received the Nobel Prize for research on the mechanisms of cell aging and the discovery of telomerase, meditative techniques have a positive effect on the length of telomeric sites and the activity of this enzyme.
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