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![Telomerase Extends Cell Life Span
and Overcomes the Hayflick Limit
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140 ] hTERT +
Population Doublings
Cells have Telomerase
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Cells have No Telomerase
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Slide courtesy of Woody Wright, Ph.D.](https://image.slidesharecdn.com/tasciencespresentationoct302012-121121153652-phpapp01/75/Ta-Sciences-How-TA-65-can-Help-You-Today-29-2048.jpg)
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Ta Sciences - How TA-65 can Help You Today!
Telomerase Activation: The Key to Unlocking the Aging Puzzle The presentation discusses telomeres and telomerase, and their role in cellular aging and longevity. It notes that telomeres protect chromosome ends and shorten with each cell division, acting as a biological clock for aging. Telomerase is an enzyme that can rebuild telomere length, counteracting their shortening. Studies show telomerase activation can rejuvenate cells and tissues in mice, reducing biomarkers of aging without increasing cancer risk. Preliminary human studies suggest telomerase activation may provide benefits like improved immunity and bone density. The presentation promotes further research on telomerase activation as a way to potentially treat aging and age-related diseases
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Ta Sciences - How TA-65 can Help You Today!
- 1. Telomerase Activation: TheKey to Unlocking the Aging Puzzle Presentation by: Noel Thomas Patton Founder and Chairman Telomerase Activation Sciences, Inc.
- 2. The Nobel prizein medicine was awarded in 2009 for the discovery of telomerase. There are over 8,000 scientific publications regarding telomeres & telomerase. Telomeres are critical sequences of DNA because they protect all the other DNA on the chromosomes 2010 study at Harvard Medical School shows telomere shortening to be a root cause of cellular aging and mitochondrial degradation. Age related decline, dysfunction, and a shortened lifespan are all related to telomere shortening.
- 3. • Repetitive DNAsequences (six-nucleotide TTAGGG) at the ends of chromosomes • In a human cell there are 46 chromosomes, 23 from your mother and 23 from your father. So each cell has a total of 92 telomeres (one at each end)
- 10. • Serve aschromosome end-caps to protect the integrity of our genes. • Keep chromosomes from degrading to prevent fusion and massive genomic instability. • Allow cells to replicate (cells can not divide when telomeres get too short) Bottom Line: Telomeres protect cells from DNA mutations, senescence and death.
- 11. Somatic (body) cells › make up more than 99% of the cells in the adult body . › have little or no telomerase and telomeres shorten as we get older. Telomere Length Shortening: › Conception: Our telomeres start out 15,000 base pairs (bp) long. › By Birth the embryo has divided so many times that telomere length is down to 10,000 bp. › Over the rest of our lifetime we lose another 5,000 to 7,000 bp. › When telomere length gets down to 3-5,000 bp, the genome is no longer protected from mutations, the cell can no longer divide, becomes scenescent, metabolism slows down, and the cell dies.
- 12. Telomeres are the Biological Clock of Aging • Telomere shortening regulates how many times a cell can divide and signals changes in gene expression to an older phenotype. • Telomeres shorten each time a somatic (body) cell divides. This is the aging clock. • When telomeres get too short, cells can no longer replicate and they become old (senescent) or die. • Telomere length represents your biological age as opposed to chronological age.
- 14. Telomere Length vs.Cellular Age Population Doublings Time Slide courtesy of Woody Wright, Ph.D.
- 15. When Cells Divide, Telomeresget Shorter…
- 16. …and can nolonger protect the chromosome
- 18. Journal of American Medical Association (JAMA) reported a study that followed 800 people for 10 years and found that people with the shortest telomeres were 11 times more likely to die of cancer than people with the longest telomeres: 11 times is statistically huge! Telomere Length and Risk of Incident Cancer and Cancer Mortality JAMA. 2010;304(1):69-75.
- 19. People with shorter telomeres in their immune cells had twice the risk of death from heart failure as patients with the longest telomeres. From A study sponsored by the American Heart Association (2008) Farzaneh-Fal et al. “Prognostic Value of Leukocyte Telomere Length in Patients With Stable Coronary Artery Disease: Data From the Heart and Soul Study.” Arteriosclerosis, Thrombosis & Vascular Biology. 2008. 28(7):1379-1384. "Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers." Telomere Dysfunction: A Potential Cancer Predisposition Factor (2003)J National Cancer Inst. 2003 Aug 20;95(16)1211-18. Wu X, Amos CI, et. Al Fraternal twins with the shortest telomeres had a three times greater risk of death during the follow-up period than their co-twins with the longest telomere measurements Telomere length predicts survival independent of genetic influences (2007) Stephanie L. Bakaysa, Lorelei A. Mucci, P. Eline Slagboom, Dorret I. Boomsma, Gerald E. McClearn, Boo Johansson and Nancy L. Pedersen. Aging Cell, 2007.
- 21. The disease ofshort telomeres
- 22. Low Telomerase/ Telomere Shortening Accelerated Aging Cell Senescence Inflammatory Damage Loss of Tissue Function Degenerative Disease Cancer
- 23. Lead a healthy lifestyle Activate Telomerase
- 24. TELOMERASE is a natural enzyme that stabilizes telomere length by adding DNA repeats (TTAGGG ) onto the telomeric ends of the chromosomes, thus compensating for the erosion of telomeres when cells divide.
- 25. Telomerase Telomere Telomerase
- 26. Telomerase Telomere hTERT hTR template Telomerase is a molecular motor that adds new DNA onto the ends of telomeres Slide courtesy of Woody Wright, Ph.D.
- 28. Telomerase prevents telomere shortening and cellular replicative senescence. Telomerase makes cells live longer and bypass the Hayflick Limit. Telomerase causes cells to revert to a younger phenotype. That means cells actually become younger!
- 29. Telomerase Extends CellLife Span and Overcomes the Hayflick Limit 160 140 ] hTERT + Population Doublings Cells have Telomerase 120 100 80 ] hTERT - Cells have No Telomerase 60 40 0 50 100 150 200 250 300 Days Slide courtesy of Woody Wright, Ph.D.
- 30. Telomerase Prevents AndReverses Telomere Shortening
- 33. 10,000 genes on a chip Young Old Telomerized (notice overall changes) (rejuvenated to “Young”) Actual data in: Funk et al, Exp Cell Res, 2000
- 34. Short Telomeres Gray and Thinning Hair These Mice are Weakened Immune System the Same Age! Intestinal Atrophy The one on top Reduced Spleen Size has no Decreased Wound Healing telomerase. Decreased Lifespan! Long Telomeres Rudolph, et al Cell 1999 Samper, et al EMBO rep 2001 Slide courtesy of Bill Andrews
- 35. Human skin on a mouse Young Old Telomerized Slide courtesy of Bill Andrews Funk et al, Exp Cell Res, 2000
- 37. Telomerase Activation was used to change old mice back to young adults. Brain, spleen and reproductive organs were all rejuvenated; Resulting in increased neurons and new viable sperm cells. Sense of smell returned. None of the mice developed cancer. Harvard Nov 2010 DePinho et al
- 38. There is a whole class of diseases caused by short telomeres. Short telomeres are involved with all the diseases associated with aging. Few specialists are aware of the root cause of the diseases they are treating.
- 39. • Cardiovascular • Muscular Dystrophy • Cancer • Cell & Tissue Transplants • COPD • AIDS • Degenerative Disc • Progeria Disease • Dyskeratosis Congenita • Alzheimer’s • Idiopathic Pulmonary • Osteoarthritis Fibrosis • Rheumatoid Arthritis • Cri du Chat syndrome • Osteoporosis • Down’s Syndrome • General Immunity • Fanconi’s Anemia • Skin Aging • Tuberous Sclerosis • Macular Degeneration • Werner’s Syndrome • Liver Cirrhosis • And, Aging Itself???????
- 40. TA-65 The World’s Only Telomerase Activation Product TA-65is a rare molecule discovered in a common medicinal plant. TA-65 is proven to transiently activate telomerase.
- 41. Regulatory Element Telomerase Gene
- 42. Repressor Regulatory Element Telomerase Gene
- 43. Regulatory Element Telomerase Gene
- 44. The most strikingin vivo effects were: Decline in the percent senescent cytotoxic T cells (CD8+/CD28-) at 6 and 12 months In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months were measured. There was a significant reduction in the percent of short (<4 kbp) telomeres (p=0.037) No adverse events were attributed “We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of immunocompromised subjects toward the more „youthful‟ profile of non compromised subjects…”
- 45. Short Telomeres Lengthened* Senescent CD28- T Cells reduced* Naive Cytotoxic T Cells (CD95-) increased* Bone density Improved Improved Vision Enhanced male sexual performance Better Skin Elasticity Anecdotal results: › Increased energy and athletic performance › Improved Endurance › Improved Sleeping quality *Data published in peer reviewed scientific journal Rejuvenation Research
- 47. Mice were treatedwith a single molecule telomerase activator (TA-65) and the researchers reported the in vivo effects on telomerase levels, aging and cancer. No detectable tumorigenic activity. Several improved health indicators in adult/old mice. The mechanism of action is through the rescue of short telomeres in a telomerase-dependent manner. The specific telomerase activator TA-65 impinges on targets of the MAPK pathway. “In short, this study provides proof-of-principle that health improvements are possible through treatment with a small molecule telomerase activator without any detectable deleterious effects.”
- 48. Telomere Length by Tertiles Cancer and CVD Shortest (Willeit, 2010a; Willeit, 2010b) 800 men, women, 45 to 84y, Mid tracked 10 yrs 92 cases of incidence, 44 of Longest mortality Shortest v. longest tertile hazard ratios (multivariate Shortest model) 3.1 cancer incidence Mid 11.1 cancer mortality 2.25 composite CVD end points Longest
- 49. Rejuvenation Research Journal: author, Cal Harley, Sept. 2010 Safety findings: No adverse events occurred among the subjects taking the telomerase activator “The Telomerase Activator elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence”…..author, Maria Blasco, “Aging Cell” April 2011 Over 10,000 people using TA-65, some for over 5 years, with no significant adverse effects.
- 50. No, notin the case of a total human being: TA-65 works in selected biological systems, not in every cell of the entire organism But, people who have transiently activated the telomerase enzyme, have seen statistically significant improvements in their immune system, bone density, sexual performance, and several other key areas
- 51. Thanks to: Calvin Harley Bill Andrews Woody Wright Maria Blasco for their contributions to Telomere Biology and this presentation
Editor's Notes
- #3 There is a whole class of diseases called the Telomere Syndromes. The root cause of these diseases is short telomeres, caused by lack of the enzyme telomerase. I will come back to this new emerging paradigm later, but first for the few of you who are not familiar with the science of Telomere Biology, let’s go over some basics.
- #4 There is a gene that I will call the telomerase gene, it’s scientific name is hTERT. When that gene is turned on, it causes the enzyme telomerase to be produced. TA-65 is a single small molecule that transiently turns on the hTERT gene and activates telomerase.
- #5 Let’s zoom in on this man and find telomeres.
- #9 Here we see the telomeres at the end of this pair of chromosomes. Telomeres serve as protective end caps to protect the rest of the chromosome where all our genes are located.
- #10 This is an actual photograph taken by an electron microscope. The bright spots at the ends are the telomeres.
- #11 They are like the plastic tips at the ends of shoelaces. When they unravel, their protective function is lost.
- #12 Let me give some quick definitions: There are 2 basic types of cells in our bodies. GERM cells and SOMATIC cells. GERM cells are our reproductive cells: EGGS and SPERM. Eggs are unusual since they are all made prior to birth, but sperm are continually generated so they have telomerase turned on all the time and their telomeres never get short. In fact, in sperm cells older men have slightly longer telomeres than younger men.SOMATIC cells are all the rest of the cells in our body. The telomerase gene in these cells is turned off most of the time and telomeres shorten with age. We can pass on the genes in our germ cells to our children, but when our body (scientifically referred to as the “soma”) dies, all of the genetic material in those cells dies also. It is somatic cells that we are talking about when we talk about normal human aging. Note: Stem cells are specialized somatic cells, they have some telomerase and their telomeres stay longer than ordinary somatic cells. But they still age, just not as fast. I also want to define “Base Pairs.” Base pairs are units of DNA that make up the chromosomes. That includes the TTAGGG sequence of telomeric DNAat the tips of our chromosomes that forms the telomeres.
- #13 It is important to understand that shortening telomeres do two basic things. First they determine how many times the cell can divide before reaching what is called the Hayflick limit which I will explain in a minute. Second, as telomeres shorten, signals are sent to the rest of the cell instructing it to age. As you know, we have exactly the same genes as adults as we had when we were babies. But obviously something has changed. And that is that some genes are now turned off that earlier were turned on and vice versa. This is called changes in gene expression. As we age gene expression changes to an older phenotype and these changes are signaled by shortening telomeres.
- #16 This slide shows telomeres getting shorter with each cell division.
- #17 Here you can see the telomeres shortening and fraying over multiple cell divisions until the chromosomes are no longer protected. When telomeres get too short, the result is catastrophic. Cells can no longer divide and they become senescent and die.
- #18 Here you can see cells becoming senescent and dying
- #19 Here are some examples of important recent scientific studies.The first one is a 2010 article from the Journal of American Medical Association showing an amazing statistic: people with short telomeres were 11 times more likely to die of cancer than with people with longer telomeres!
- #20 Here are 3 more articles.The first is from a 2008 article, showing twice the risk of death from heart failure for people with short telomeres. The second is from a 2003 National Cancer Institute article showing that short telomeres increase the risk of cancer.The 3rd is from a 2007 Aging Cell article showing fraternal twins with shortest telomeres had 3 times greater risk of death than their siblings with long telomeres.
- #22 These unfortunate children have a genetic defect where they only produce half as much telomerase as they should. Resulting in a significantly shortened lifespan, dying of old age before reaching 20.
- #23 We see from this extreme example that having unfortunate genetics causes age related diseases, and these diseases in turn accelerate telomere loss, creating a vicious cycle.
- #24 Do what your doctor says: Eat well, exercise, avoid stress, don’t smoke, and so on. However, this can only slow down telomere shortening. It won’t stop or reverse aging. Notice that the few people who live perfect lives with no stress, etc. still get old, deteriorate, and die.To activate telomerase it is possible to do gene therapy on cells in a lab, but that is not currently possible in live humans; for living people there is only one thing available, TA-65.
- #28 So hereis a quickreview: It is a fact that as our cells divide our telomeres shorten.It is a fact that as our telomeres shorten our cells age.It is a fact that in order to stop our aging, we must overcome our telomere shortening.How are we going to do this? By activating Telomerase.
- #29 Obviously by now we can all see that telomerase is critically important.
- #30 The solid lines at the bottom show that cells have stopped dividing after about 50 doublings. The broken lines show that when cells have telomerase, they can continure to divide indefinately. They have beaten the Hayflick Limit.
- #31 It is the lengthening of the telomeres by telomerase activation that allows cells to beat the Hayflick limit and rejuvenate.
- #32 Watch how the cells that have telomerase activated rejuvenate and continue to divide as healthy functioning cells.
- #33 These hands are from the same person and contain the exact same genes, so why are they so different? The answer is because of gene expression.Genes are expressed by being turned on or turned off. When we are young, some genes are on and others are off. As we age, gene expression changes and the phenotype changes from young to old.
- #34 Here we can see how adding telomerase changes gene expression back to a younger phenotype.
- #35 The mouse on top has no telomerase, the mouse below does. The mouse without telomerase suffers from grey and thinning hair while the telomerized mouse has a thick and youthful coat. Other differences are weakened immune system, intestinal atrophy, reduced spleen size, decreased wound healing, and a shorter lifespan.
- #36 On the left is a depiction of young healthy skin, in the middle you can see weakened skin due to ageing, and on the right, with telomerase activated, the skin reverts to a younger phenotype.
- #37 A major milestone in scientific research was achieved in 2010 with the publication of the above article in the prestigious scientific journal Nature. This paper indicates that normal human ageing could be slowed by activating (reawakening) the telomerase enzyme in cells where it has stopped working. The lead author, Dr. Ronald DePinho of Harvardsays, "This has implications for thinking about telomerase as a serious anti-ageing intervention.“
- #38 This was the first time in history showing aging reverse in a mammal. These striking results were unexpected. The researchers were expecting a slowing or a stabilization of the aging process. Instead, there was a dramatic reversal in the signs and symptoms of aging with telomerase activation. "If you look at all those data together, you walk away with the idea that the loss of telomerase could be a very important instigator of the ageing process," says DePinho.And this was accomplished by activating telomerase. Telomere Science is about to rapidly change the medical landscape.
- #39 An important paper by Nobel laureate Elizabeth Blackburn published in Nature Reviews in October 2012 introduces the concept of The Telomere Syndromes.The paper discusses a whole category of diseases caused by critically short telomeres. She calls these diseases The Telomere Syndromes.Virtually all diseases of aging fall under the category of Telomere Syndromes.Few specialists are aware of the root cause of the diseases they are treating is shortening telomeres.
- #40 These are some of the diseases under the class of Telomere Syndromes, as you can see, the list is long and includes most of the diseases of aging.
- #41 By now, it should be clear to everyone in this room that shortening telomeres are the root cause of aging, I call it the “kiss of death”. The question is what can be done about it besides leading a healthy life style? The only answer currently available is TA-65.
- #45 There are two critical things that TA-65 has been shown to do in published papers. A 2010in-vivo human study published in Rejuvenation Research showed: 1) Lengthening of the Shortest Telomeres. (These are the ones that really matter; it only takes one short Telomere out of the 92 in every cell to send a cell into crisis) 2)Improved Immune system remodeled toward a more ‘youthful’ profile: Specifically the number of senescent CD28- T Cells significantly decreased. This is a reversal of what normally happens with age.
- #46 Here is a more complete list of significant benefits that were seen in that study. These human results will be published in a follow-up paper.
- #47 These graphs show some of the results of a double blind, placebo controlled study done in 2005. TA Sciences is now doing another larger double blind, placebo controlled, one year long study that will be published early in 2014.
- #48 When you combine human data with mice data the evidence is strong that TA-65 produces significant health benefits without increasing cancer risk.
- #49 We need to keep telomeres long.Short telomeres contribute to cancer and cardiovascular disease. These are just 2 of the Telomere Syndrome diseases.
- #50 I often get asked about cancer. Will TA-65 possibly accelerate malignant transformation of cells? The answer is just the opposite. Major factors in cancer formation are the mutations, double strand breaks, and chromosomal fusions that occur when telomeres get too short. There are more than 10,000 people taking TA-65 with no reported serious adverse events. It appears that TA-65 may be preventing malignant transformation. While I can not say that TA-65 will cure or prevent cancer, I can say that it absolutely will not cause it.(if time permits, mention how some doctors are treating cancer patients withTA-65, not officially for their cancer, but to rebuild their immune system that has been destroyed by the body’s fighting the disease and by radiation and chemotherapy treatments.)
- #51 The data from current TA-65 users has been evaluated scientifically by Calvin Harley, PhD. and clinically by Joseph Raffaele, M.D.
- #52 If you have any questions, please do not hesitate to ask.