Researchers at MD Anderson have identified a molecule that diminishes age-related inflammation and enhances brain and muscle function in preclinical models.
Researchers at The University of Texas MD Anderson Cancer Center have shown that therapeutically restoring ‘youthful’ levels of a specific subunit of the telomerase enzyme can significantly reduce the signs and symptoms of aging in preclinical models. If these findings are validated in clinical trials, they could have important therapeutic implications for age-related diseases such as Alzheimer’s, Parkinson’s, heart disease, and cancer.
The study, published in Cell, identified a small molecule compound that restores physiological levels of telomerase reverse transcriptase (TERT), which normally is repressed with the onset of aging. Maintenance of TERT levels in aged lab models reduced cellular senescence and tissue inflammation, spurred new neuron formation with improved memory, and enhanced neuromuscular function, which increased strength and coordination.
The researchers show that TERT functions not only to extend telomeres, but also acts as a transcription factor to affect the expression of many genes directing neurogenesis, learning and memory, cellular senescence, and inflammation.
“Epigenetic repression of TERT plays a major role in the cellular decline seen at the onset of aging by regulating genes involved in learning, memory, muscle performance, and inflammation,” said corresponding author Ronald DePinho, M.D., professor of Cancer Biology. “By pharmacologically restoring youthful TERT levels, we reprogrammed expression of those genes, resulting in improved cognition and muscle performance while eliminating hallmarks linked to many age-related diseases.”
Loss of TERT is connected with aging through multiple mechanisms
Aging is associated with various epigenetic changes that influence functional and physiological decline. One of the hallmarks of aging is the gradual shortening of telomeres, the chromosomal end structures that help maintain their stability. Free radicals also can modify and harm telomere sequences.
When telomeres become extremely short or modified, they trigger a continual DNA damage response, which can lead to cell senescence – a phenomenon in which cells release inflammatory factors that can cause tissue damage, prompting aging and cancer.
Telomerase is a protein complex responsible for synthesizing and extending telomeres. However, its activity is reduced over time due to the epigenetic silencing of TERT, particularly at the onset of natural aging or Alzheimer’s and other age-related diseases.
The DePinho laboratory previously showed that deactivating the TERT gene in vivo led to premature aging, which could be reversed through TERT reactivation. The researchers also observed that certain cells, such as neurons and cardiac cells, were rejuvenated without undergoing the normal cell division required to synthesize telomeres.
Their observations led them to hypothesize that TERT had other functions beyond synthesizing telomeres and that overall telomerase levels were important in the aging process. Based on these findings, the researchers, led by DePinho and first author Hong Seok Shim, Ph.D., aimed to develop a drug to restore TERT levels.
Small molecule restores TERT levels, reversing hallmarks of aging
A high-throughput screen of over 650,000 compounds identified a small-molecule TERT activating compound (TAC) that epigenetically de-represses the TERT gene and restores physiological expression present in young cells.
In preclinical models equivalent to adults over age 75, TAC treatment for six months led to new neuron formation in the hippocampus (memory center) and improved performance in cognitive tests. Additionally, there was an increase in genes involved in learning, memory, and synaptic biology, consistent with TERT’s ability to interact with and control the activity of transcription factor complexes regulating diverse genes.
TAC treatment also significantly reduced inflammaging – an age-related increase in inflammatory markers linked with multiple diseases – in both blood and tissue samples and also eliminated senescent cells by repressing the p16 gene, a key senescence factor.
TAC improved neuromuscular function, coordination, grip strength, and speed in these models, reversing sarcopenia – a condition under which muscle mass, strength, and performance naturally worsen with advancing age.
Additionally, TAC treatment in human cell lines increased telomere synthesis with reduced DNA damage signal at telomeres and extended the proliferative potential of these cells, demonstrating the activity of TAC in ex vivo human models.
“These preclinical results are encouraging, as TAC is easily absorbed by all tissues, including the central nervous system. Yet further studies are needed to properly assess its safety and activity in long-term treatment strategies,” DePinho said. “However, our deeper understanding of the molecular mechanisms driving the aging process has uncovered viable drug targets, allowing us to explore opportunities to intercept the causes of a variety of major age-related chronic diseases.”
Reference: “TERT activation targets DNA methylation and multiple aging hallmarks” by Hong Seok Shim, Jonathan Iaconelli, Xiaoying Shang, Jiexi Li, Zheng D. Lan, Shan Jiang, Kayla Nutsch, Brittney A. Beyer, Luke L. Lairson, Adam T. Boutin, Michael J. Bollong, Peter G. Schultz and Ronald A. DePinho, 21 June 2024, Cell.
DOI: 10.1016/j.cell.2024.05.048
This study was supported by the National Institutes of Health (R01 CA084628, P30 CA016672, and S10 RR029552), the G. Harold and Leila Y Mathers Charitable Foundation, and the Belfer Family Foundation Neurodegeneration Consortium. This study was a collaborative effort with Peter Schultz and Michael Bollong at the Scripps Institute.
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28 Comments
Very Interesting.
Treatment of the signs of aging after the fact, is different from prevention of aging itself in the first place.
Cell replacement Therapy is one strategy. Prevention of existing Cells from the effects of aging is another strategy. Controlled reversal of Aged Cells is the third strategy. Doing so under controlled conditions so that Cell Growth is not uncontrolled resulting in Cancer.
Cancer drivers can be internal or external. Treatment would require determination of the root cause of the uncontrolled growth of cells and suppressing it and bringing it control.
Aging itself can be thought of as the Cell functioning being impaired in the long term.
More Info, are there and study were i can join
Almost all cancer drivers are external in the form of diet and environmental but overwhelmingly diet.
It would be great if science and medicine quit running interference for the food industry which is mostly owned by tobacco companies.
Agreed. However there is another component contributing to cancer besides toxic food and toxic environment; toxic emotion. Unresolved anger, frustration, and resentment create a foundation within that is a suitable environment for toxic homesteading. We tend to stuff down and try to forget these. That is not resolution. Self deception takes ethical considerations out of play when assigning blame; the root of anger frustration and resentment taking up residence within. I am a doctor of traditional Chinese medicine.
Who do I contact About getting this here is Mexico?🤠
Or in Texas?
This information is excellent. Many thanks
Always the same. “Big discoveries” and nothing comes of it.
They need to get AI helping them as in this article:
—-
AI saves researchers years in finding a better green hydrogen catalyst
By Abhimanyu Ghoshal
September 02, 2024
https://newatlas.com/science/ai-better-green-hydrogen-catalyst/
Hope experiment go well, and ordinary people could benefit of it.
Who do I contact to get this?
I would love to try this my body is full of Inflammation
I pray it helps
The full efficacy of this should be ready in about – – 40 years or so. It’s going to take awhile for Big Pharma to lock in their colossally obscene profit structure via the proper regulatory capture. After all, they need to structure treatments, not generate cures. Cures do not maximize profits for the shareholders.
All B.S. nothing comes out of these studies…….they only people that benefit are these so call scientists who do nothing for humanity and get paid for a doing nothing job they have.
Thanks for this information. How soon clinical trials will be available?
No name or identification of this compound other than ‘TAC’. Hmm.
Well it’s just N-(4-Chloro-3-fluorophenyl)-4,6-dimethyl-2-(methylsulfonyl)pyrimidin-5-amine! What, you didn’t know that?
https://www.medkoo.com/products/58532 CAS 666699-46-3 However, It should be noted that the body uses accelerated aging of cells that have accumulated mutations as a defense against oncology. Therefore, the use of drugs like TAC can cause the proliferation of precancerous cells. The human body lives much longer than the body of mice (on which the effect of TAC was tested), therefore chronic use of TAC is tens of times more dangerous for humans than for mice. https://pubmed.ncbi.nlm.nih.gov/37863351/
Or, or, maybe stop eating garbage? Garbage in garbage out and you don’t even have to do any research to know that.
It seems to me like the scientists are all self-serving. We know what causes 90% of the diseases Americans are suffering and it’s their diet.
Why don’t you hear any of these scientist cowards talking about that?
Haha! I feel the same way you do, Dave—stop eating garbage! That’s all you need to do to promote longevity through aging.
I’m in stage IV colon cancer. Had CABAGE x 5. Currently being treated at MD Anderson for 2 years now. Dr. Morris is my Oncologist. Always great work going on at MD Anderson.
Exactly 💯 agreeing have have been doing my own study on myself the results are crazy from eating a year of junk food then a year of food healthy not the healthy that we have all been thought either the Gundry healthy way and taking pictures of me before me after and this is so true I have done study on myself four the last five years since having my 15 surgery in my 42 years on this earth the 39 years first starting at age 15 and lasting until 39 and me having enough of being there Ginapig is all they wanted to do was cut on me open me up no more not this women I found that if you eat proper and take CBD PASTE ALONG with Dr gundry’s vital reds, bio complete3, and lectin sheild it helps to grow back damaged parts your body starts to regrow at least for me it did there is one more thing you have to take but no one would ever believe me because i didnt finish my education i became a mom instead
Please do a study on the benefits of this with long Covid. It could be a life changer for thousands.
This is exactly the enzyme in sweet potatoes and the substrate used in the brain to repair is phosphotidy serine .
Take both daily and exercise .
Big pharma will hide it .
It has remarkable brain repair and Alzheimer’s reversal. Both .together .
Thanks Karen! Could you please add some supplemental information about what you perceive as more optimal doses or symbiotic ratios of the sweet potatoes and phosphotidy serine? Your insights would be worth considering. Thanks so much in advance. Paul
https://www.google.com/url?sa=t&source=web&rct=j&opi=89978449&url=https://draxe.com/nutrition/phosphatidylserine/%23:~:text%3DPhosphatidylserine%2520is%2520considered%2520safe%2520when,include%2520insomnia%2520and%2520upset%2520stomach.&ved=2ahUKEwityu2Bn6mIAxWa5MkDHY9EOlcQFnoFCK0BEAU&usg=AOvVaw2cfcqN9f9lnlj9rwnZTGXs.
The solution to severely decreasing or completely stopping most the effects of aging has been researched by global pharma and many unknown brilliant scientists around the world. They have a solution(s). The discussions taking place now are concerning economics (which government, individuals, pharma profits and how much) supply chain, & distribution and how to determine who qualifies. A whole new social class will be created if upper middle class and below have complete access to the med, financial status irrelevant. Unfortunately, based human behavioral history, the wealthy and powers that be will not release until every revenue opportunity is exhausted. That’s what I would do. That’s what I was I taught to do
A final thought. What do you with a billion homeless people who can live 300 years? We really need to think about that. I’m sure it’s being discussed as we speak.