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From doing business with your telomeres to start practising Zen meditation

Telomeres can listen to you

From doing business with your telomeres to start practising Zen meditation
Photo by Adam Wilson on Unsplash

“To an extent that has surprised us and the rest of the scientific community, telomeres do not simply carry out the commands issued by your genetic code. Your telomeres, it turns out, are listening to you. They absorb the instructions you give them. The way you live can, in effect, tell your telomeres to speed up the process of cellular aging. But it can also do the opposite.”The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer by Dr. Elizabeth Blackburn and Dr. Elissa Epel

Telomeres and Telomerase

Every single cell in your body — apart mature red blood cells and cornified cells in the skin, hair and nails — has a nucleus. Every nucleus contains 23 pairs of chromosomes (haploid genome), for a total of 46 chromosomes (diploid genome). Every chromosome is made of a very long strand of DNA — tightly wrapped around proteins — that contains many genes that determine your traits. At each end of your chromosomes you can find the telomeres.

Every telomere is a region of repetitive nucleotide sequences which protects the end of your chromosomes from deterioration or from fusion with neighbouring chromosomes, protecting the encoding DNA during chromosome replication.

However, your telomeres they don’t contain active genes but instead they contain an array of highly repeated DNA sequences and specific binding proteins that form a unique structure at the end of your chromosomes, something like a little cap.

The enzyme responsible for the maintenance of the length of your telomeres  its called telomerase. The telomerase can be found in fetal tissues, adult germ cells and also tumor cells, while the telomerase activity is regulated during development and has a very low, almost undetectable activity in somatic (body) cells.

Moreover, the telomere maintenance relies on a vast network of protein complexes, and central to this process is a six-protein complex known as the telosome or shelterin. It is believed that the “shelterin” complex stabilizes a structure named the telomere-loop (or t-loop for short) with the purpose of shielding the exposed end of linear chromosomes.

In your somatic cells the proliferation potential is strictly limited and approximately 50 nucleotides are lost during each cell cycle, which results in gradual telomere length shortening. Critically short telomeres cause senescence (irreversible cell-cycle arrest) and eventually cell death.

In particular, the telomere shortening to a critical length can trigger aging and shorter life spans (both in mice and humans), by a mechanism that involves induction of a persistent DNA damage response at the chromosome end, and eventually loss of cellular viability. And that is something that the longevity industry and its anti-aging crusade is trying to resolve.

However, the opposite, namely very long telomeres is also a bad thing. In actual fact, in cancer cells the enzyme telomerase is triggered preventing telomere shortening, so the cells can divide indefinitely...and this is bad news for cancer patients.

For example, a new study (appeared in eLife) described that cancer-prone families with unique TINF2 mutations — a shelterin subunit that controls telomere length — had lymphocyte telomeres unusually long (lymphocytes are one of the body's main types of immune cells). Further data suggested that the TINF2 mutations predisposed these families to a tumor syndrome (breast cancer, colorectal cancer, melanoma and thyroid cancers), tumors that would normally have been blocked by telomere shortening.

But why do our telomeres shorten?

Most of our somatic cells lack the activity of the enzyme telomerase and during cell division they experience a phenomenon called the “end-replication problem”. This occurs due to the intrinsic inability of DNA polymerases — the master enzyme for the synthesis of new DNA molecules — to completely replicate the telomere C-rich lagging-strand, so the newly synthesized strand will inevitably be a few nucleotides shorter, resulting in loss of telomere repeats.

Now here’s where some business guys out there spotted a business opportunity and said “let’s find a way to keep telomeres from getting shorter and eventually stop aging”. And this of course is an idea that sounds very interesting to old rich people with a lot of money to invest.

Nevertheless things are more complicated (and not so business-linear) when planning to play around with telomeres, since the ultimate debate: "Short telomeres, shorter life spans and less cancer" or "Long telomeres, longer life spans but more cancer" is just inevitable.

If truth be told, us humans have relatively short telomere lengths (5 to 15 kb) and yet humans have much longer life spans than mice that have telomere lengths around 50 kb and a shortening rate of 7,000 bp per year. And that is probably indicating that is the different rate of telomere shortening between us and mice that could explain the different longevities between the two. In other words, is not just "Pick up a long or a short telomere".

For example, in a study published in PNAS in 2019 scientists measured in parallel the telomere length of a wide variety of species (birds and mammals) with very different life spans and body sizes — including mouse, goat, Audouin’s gull, reindeer, griffon vulture, bottlenose dolphin, American flamingo and Sumatran elephant — and they found that the telomere shortening rate — “but not the initial telomere length alone” — is a powerful predictor of a specie’s life span.

For this reason (or debate called it what you want), scientists started to genetically manipulating the telomerase enzyme in mice. And even though they have found conflicting results, just one study found that overexpression of the telomerase in adult mice led to a 24% increase in median lifespan while not increasing the incidence of cancer. Therefore, the idea of activating telomerase as anti-aging therapy became a powerful one: "Let's make a pill and take it every morning to lengthen our telomeres".

For this reason, Elizabeth (Liz) Parrish the CEO of BioViva— a biotechnology company that focuses on developing gene therapies and other regenerative therapies to intervene with human aging — became the patient zero for two anti-aging therapies that the company is researching: a telomerase gene therapy and a myostatin inhibitor, which is expected to prevent age-associated muscle loss. So far the company has claimed the experiments were successful in lengthening Liz's telomeres, though results were never published.

Sierra Sciences, LLC a biotechnology company founded in 1999 in Reno, Nevada by William H. Andrews — former director of molecular biology at Geron Corporation — is also working on telomerase activation with the goal of preventing and/or reversing and ultimately curing diseases associated with human aging, including the aging process itself, with telomerase-activating compounds. They claim to have screened 250000 compounds so far, with TAM-818 being the most potent inducer of telomerase on the planet.

Telocyte, is also working on telomerase activation for Alzheimer’s disease, with Telocyte and CNIO (Spanish National Research Centre) collaborating to take Telomerase Therapy to FDA human trials. Libella Gene Therapeutics — based in Manhattan, Kansas — claims also it is now offering a gene therapy to repair telomeres at a clinic in Colombia for $1 million a dose. The company announced on November 21, 2019 that it was recruiting patients into what it termed a “pay-to-play clinical trial”, to inject patients with viruses carrying the genetic instructions cells need to manufacture telomerase. The dangers of this kind of experiment are enormous — because there is a risk of activating a pre-cancerous cell that already have all the alterations except telomerase — but despite this right now they have three clinical trials actively recruiting (targeting Alzheimer Disease, Aging, Critical Limb Ischemia) all outside US.

There’s another company called T. A. Sciences founded in 2002 that claims to be the leader in the field of cellular rejuvenation and age management through telomerase activation. The company’s product is based on the cellular rejuvenation properties of a herbal extract compound called TA-65®.

TA-65 is a dietary supplement based on an improved formulation of a small molecule telomerase activator that was discovered in a systematic screening of natural product extracts from traditional Chinese medicines.

Studies suggested that TA-65 can lengthen telomeres in a statistically and possibly clinically significant manner. The TA-65 supplement itself is ridiculously expensive, but most importantly a lawsuit challenged their anti-aging claims. In fact, the Federal Trade Commission charged T. A. Sciences, Inc. and Noel Patton (collectively, TA Sciences) with lacking the scientific evidence to support claims that their products could provide a broad range of anti-aging and other health benefits.

Moreover, it would appear that if you avoid stress, junk food, smoking (oxidative stress in general) and you keep fit and adopt a Mediterranean diet you can protect your telomeres from shortening in a natural way.

In particular, several studies indicated that telomeres' length is positively associated with the consumption of legumes, nuts, seaweed, fruits, 100% fruit juice, dairy products and coffee, whereas it is inversely associated with consumption of alcohol and processed meat. It is therefore possible that nutrients regulate telomere health by regulating oxidative stress and systemic inflammation.

But apart systemic inflammation from food and smoking, scientists are also finding that several thought patterns appear to be unhealthy for your telomeres, and some of them are

  • cynical hostility,
  • pessimism,
  • rumination and
  • thought suppression, the attempt to push away unwanted thoughts and feelings.

So, could your thoughts make you age faster by affecting your telomeres?

Apparently yes, and this is coming from Elizabeth Blackburn, a woman that has evolved from a “Lab rat” to a “Wonder woman” after she discovered the molecular structure of telomeres and co-discovered the enzyme telomerase, and eventually won the Nobel Prize in Physiology or Medicine 2009 — jointly to Carol W. Greider and Jack W. Szostak — for the discovery of telomeres and the enzyme telomerase.

In particular, the association of anger and hostility with future coronary heart disease was investigated in a meta-analysis review, suggesting that anger and hostility are associated with coronary heart disease outcomes both in healthy and coronary heart disease populations.

In another study, the combination of less positive and more negative expectations for the future (i.e., lower optimism and higher pessimism) increased the risk for disease and early mortality, suggesting that pessimism may increase an interleukin — a molecule that acts both as a pro-inflammatory cytokine and an anti-inflammatory myokine (IL-6) — and eventually accelerate the rate of telomere shortening, as it was indicated by examining 36 healthy post-menopausal women.

Furthermore, when examined the daily stress responses in healthy women who were family caregivers, the more the women ruminated after a stressful event the lower the telomerase was in their aging CD8 cells — namely the immune cells that send out proinflammatory signals when they are damaged. In fact, people who ruminate, experience more depression and anxiety which are in turn associated with shorter telomeres.

And finally, in a small study it was demonstrated that greater avoidance of negative feelings and thoughts — the opposite of mindfulness referred as awareness that emerges by intentionally focusing on the present experience in a non judgmental or evaluative manner — was also associated with shorter telomeres. However, the psychological mechanisms underlying this potential relationship are unknown, but yet practising Zen meditation —a technique similar to mindfulness in that it’s about focusing on the presence of mind — is associated with longer leukocyte telomere length.

"The goal of meditation is not to control your thoughts. it's to stop letting them control you".

aging
Marina T Alamanou
Marina T Alamanou
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Marina T Alamanou

Marina T Alamanou

Life Science Consultant

Life Science Content Creation

https://www.linkedin.com/in/marina-t-alamanou-665bb013a/

@MetaphysicalCells

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