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“I want LONGER Telomeres”
                             Oprah Winfrey -November 1st, 2007

                   Long
                 Telomeres




       Short
     Telomeres
Telomere Biology:
  The Emerging Paradigm Shift


             Presentation by:

        Noel Thomas Patton
           Founder and Chairman

Telomerase Activation Sciences, Inc.
              Revised Feb. 3, 2010
Telomere Biology:
 A Remarkable Breakthrough in Medicine

• 2009 Nobel Prize in medicine awarded for
  discovery of telomerase
• Telomeres are the single most important sequences
  of DNA because they protect all the other DNA on
  our chromosomes
• Short telomeres are associated with almost every
  affliction of old age
• Long Telomeres are associated with healthy aging
  and longevity
Hayflick Limit
Population Doublings




                              Time
                                        Slide courtesy of Woody Wright, Ph.D.
Telomere Length vs. Cellular Age
• Somatic Cells generally have little or no telomerase and
  telomeres shorten as we get little older
  Conception: Our telomeres start out 15,000 base pairs long

  By Birth the embryo has divided so many times that
  telomere length is down to 10,000 base pairs

  Over the rest of our lifetime we lose another 5,000 base
  pairs and when they get down to roughly 3-5,000 most of us
  will be dead!
Bottom Line:
Short Telomeres = the “Kiss of Death”

• 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.


• 100 year olds in good health had “significantly
  longer” telomeres than those with health
  problems. Study reported in Journals of Gerontology (2008) Delara et al. “Association
   of Longer Telomeres With Better Health in Centenarians.” The Journals of Gerontology Series A: Biological
   Sciences and Medical Sciences. 208. 63:809-812.
What can be done to keep
       telomeres long?

• Lead a healthy lifestyle

• Activate Telomerase
What is Telomerase?

• TELOMERASE is an enzyme that confers
  longevity to cells

• It does this by lengthening telomeres

• Activating Telomerase will extend the life
  of cells beyond the Hayflick Limit
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.
Telomerase Extends Cell Life Span
and Overcomes the Hayflick Limit
                        160



                        140                                                        ]   hTERT
                                                                                               +

                                                                                       Cells have Telomerase
                        120
 Population Doublings




                        100



                                                                                   ]
                                                                                                -
                         80
                                                                                        hTERT

                                                                                   Cells have No Telomerase
                         60



                         40



                              0   50   100   150          200   250         300

                                                   Days
                                                                      Slide courtesy of Woody Wright, Ph.D.
Telomerase can be turned on
        with a nutraceutical
• 2000: The              Corporation discovered TA-65
  a single molecule that turns on Telomerase

• 2002: T.A. Sciences exclusively licensed TA-65 from
  Geron

• 2007: TA-65 commercialized as a nutraceutical
  capsule through licensee doctors
How does TA-65 Work?

TA-65 activates telomerase in certain cells
and lengthens telomeres and/or slows their
rate of loss.

This allows cells to live longer in a more
“youthful” state.
Schematic of cell rejuvenation using
             hTERT:

           Gene Expression Comparison:

                         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
Is TA-65 the “Fountain of Youth”?



• No, not in the case of a total human being: TA-65
  activates telomerase in selected biological systems, not in
  every cell of the entire organism

• But, TA-65 users have seen statistically significant
  improvements in their immune system, bone density,
  sexual performance, and several other key areas
Is it the “Holy Grail?”



• Maybe. For the first time in mankind’s age-old quest,
  something has the potential to extend maximum human
  lifespan

• When cells in a petri dish in the lab have a constant supply
  of TA-65, the Hayflick limit is extended and death from
  old age is delayed
Telomerase can do some pretty
              powerful things
  Short Telomeres
                                                      Gray and Thinning Hair
                                                      Weakened Immune System
                                                      Intestinal Atrophy
 These Mice                                           Reduced Spleen Size
                                                      Decreased Wound Healing
    are the                                           Decreased Lifespan!

  Same Age!
The one on top
    has no
 telomerase.
  Long Telomeres                                     Rudolph, et al Cell 1999
                                                     Samper, et al EMBO rep 2001

                    Slide courtesy of Bill Andrews
Skin Reconstitution:
  Old Cells Become Young
          Human
          skin on
          a mouse

Young           Old                      Telomerized




        Slide courtesy of Bill Andrews
        Funk et al, Exp Cell Res, 2000
Broad Potential for Tissue System
          Regeneration
Immune cells – memory and naïve
Hematopoietic stem cells
Lung alveolar cells
Skin – dermis, epidermis, vasculature
Vascular intima (endothelium)
Osteoblasts, MSCs
GI track epithelial cells
Liver – hepatocytes
Retinal pigmented tissue of eye
Chondrocytes
Skeletal muscle
Kidney – cortex
*Cardiomyocytes
*Neural cells
           *No significant bulk telomere loss, but still a protective effect of telomerase activation.
                                       Harley, Current Mol Med., 2005
                                 Garcia, Wright, Shay, Nucl. Acid Res., 2007
                               Aviv, Hypertension, 2009; Calado, NEJM, 2009
                                 Slide courtesy of Calvin Harley, Ph.D. 2010
Who takes TA-65?
• Knowledgeable professionals capable of determining
  risk/reward ratios
• About half of our clients are MD’s or PhD’s
• Several are well known Telomere Biologists


          Who should take TA-65?
• Anyone over 40 who wants to intervene in age
  related decline
• Particularly those who have measured their
  Telomeres and found them to be short
Telomerase and Cancer:
• The Red Herring: Pre-cancerous cells result from a minimum of 4
  specific genetic mutations that cause a loss of growth control.
  Because these cells are rapidly dividing, their telomeres soon
  become short and they will die. But if a further mutation occurs
  that permanently activates telomerase, the cell will become
  immortal and fully cancerous.
• This relationship of telomerase to cancer has caused some
  biologists to fear telomerase activators. But telomerase is not an
  oncogene, it simply is a mechanism to allow cells to live longer.
  That is exactly what is required if a person wants to extend their
  lifespan. The vast majority of our 10 trillion cells are healthy and
  never lose growth control. Obviously to increase lifespan, our
  healthy cells have to live longer.
Safety
• 5 years of development and safety testing
  before introducing TA-65
• Hundreds of clients taking TA-65
• Some for as long as 3 years
• Not a single adverse reaction reported by
  our licensed physicians
• Not a single diagnosis of new cancer
• Not a single report of increased cancer load
  for clients who already had cancer
Verified by Independent research
People currently taking TA-65
               have seen the following results*
• 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)
• Improved Immune system: In particular the % and absolute
  number of senescent CD8+/28- cells has significantly decreased.
  This is a reversal of what normally happens with age
• Improved bone density
• Improved cardiovascular and hormonal biomarkers that normally
  show decline with age
• There are also anecdotal results, such as improved energy and
  athletic performance, but these effects are not universal and vary
  among individuals
 *Human trial results substantiating these claims to be published in a peer reviewed scientific journal
TA-65
The Only Proven Telomerase Activating Product!


        Available through licensed doctors
                        Thanks to:

                     Calvin Harley
                     Bill Andrews
                     Woody Wright
                     Maria Blasco

               for their contributions to
         Telomere Biology and this presentation

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T.A. Sciences - Oprah

  • 1. “I want LONGER Telomeres” Oprah Winfrey -November 1st, 2007 Long Telomeres Short Telomeres
  • 2. Telomere Biology: The Emerging Paradigm Shift Presentation by: Noel Thomas Patton Founder and Chairman Telomerase Activation Sciences, Inc. Revised Feb. 3, 2010
  • 3. Telomere Biology: A Remarkable Breakthrough in Medicine • 2009 Nobel Prize in medicine awarded for discovery of telomerase • Telomeres are the single most important sequences of DNA because they protect all the other DNA on our chromosomes • Short telomeres are associated with almost every affliction of old age • Long Telomeres are associated with healthy aging and longevity
  • 4. Hayflick Limit Population Doublings Time Slide courtesy of Woody Wright, Ph.D.
  • 5. Telomere Length vs. Cellular Age • Somatic Cells generally have little or no telomerase and telomeres shorten as we get little older Conception: Our telomeres start out 15,000 base pairs long By Birth the embryo has divided so many times that telomere length is down to 10,000 base pairs Over the rest of our lifetime we lose another 5,000 base pairs and when they get down to roughly 3-5,000 most of us will be dead!
  • 6. Bottom Line: Short Telomeres = the “Kiss of Death” • 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. • 100 year olds in good health had “significantly longer” telomeres than those with health problems. Study reported in Journals of Gerontology (2008) Delara et al. “Association of Longer Telomeres With Better Health in Centenarians.” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 208. 63:809-812.
  • 7. What can be done to keep telomeres long? • Lead a healthy lifestyle • Activate Telomerase
  • 8. What is Telomerase? • TELOMERASE is an enzyme that confers longevity to cells • It does this by lengthening telomeres • Activating Telomerase will extend the life of cells beyond the Hayflick Limit
  • 9. 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.
  • 10. Telomerase Extends Cell Life Span and Overcomes the Hayflick Limit 160 140 ] hTERT + Cells have Telomerase 120 Population Doublings 100 ] - 80 hTERT Cells have No Telomerase 60 40 0 50 100 150 200 250 300 Days Slide courtesy of Woody Wright, Ph.D.
  • 11. Telomerase can be turned on with a nutraceutical • 2000: The Corporation discovered TA-65 a single molecule that turns on Telomerase • 2002: T.A. Sciences exclusively licensed TA-65 from Geron • 2007: TA-65 commercialized as a nutraceutical capsule through licensee doctors
  • 12. How does TA-65 Work? TA-65 activates telomerase in certain cells and lengthens telomeres and/or slows their rate of loss. This allows cells to live longer in a more “youthful” state.
  • 13. Schematic of cell rejuvenation using hTERT: Gene Expression Comparison: 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
  • 14. Is TA-65 the “Fountain of Youth”? • No, not in the case of a total human being: TA-65 activates telomerase in selected biological systems, not in every cell of the entire organism • But, TA-65 users have seen statistically significant improvements in their immune system, bone density, sexual performance, and several other key areas
  • 15. Is it the “Holy Grail?” • Maybe. For the first time in mankind’s age-old quest, something has the potential to extend maximum human lifespan • When cells in a petri dish in the lab have a constant supply of TA-65, the Hayflick limit is extended and death from old age is delayed
  • 16. Telomerase can do some pretty powerful things Short Telomeres Gray and Thinning Hair Weakened Immune System Intestinal Atrophy These Mice Reduced Spleen Size Decreased Wound Healing are the Decreased Lifespan! Same Age! The one on top has no telomerase. Long Telomeres Rudolph, et al Cell 1999 Samper, et al EMBO rep 2001 Slide courtesy of Bill Andrews
  • 17. Skin Reconstitution: Old Cells Become Young Human skin on a mouse Young Old Telomerized Slide courtesy of Bill Andrews Funk et al, Exp Cell Res, 2000
  • 18. Broad Potential for Tissue System Regeneration Immune cells – memory and naïve Hematopoietic stem cells Lung alveolar cells Skin – dermis, epidermis, vasculature Vascular intima (endothelium) Osteoblasts, MSCs GI track epithelial cells Liver – hepatocytes Retinal pigmented tissue of eye Chondrocytes Skeletal muscle Kidney – cortex *Cardiomyocytes *Neural cells *No significant bulk telomere loss, but still a protective effect of telomerase activation. Harley, Current Mol Med., 2005 Garcia, Wright, Shay, Nucl. Acid Res., 2007 Aviv, Hypertension, 2009; Calado, NEJM, 2009 Slide courtesy of Calvin Harley, Ph.D. 2010
  • 19.
  • 20. Who takes TA-65? • Knowledgeable professionals capable of determining risk/reward ratios • About half of our clients are MD’s or PhD’s • Several are well known Telomere Biologists Who should take TA-65? • Anyone over 40 who wants to intervene in age related decline • Particularly those who have measured their Telomeres and found them to be short
  • 21. Telomerase and Cancer: • The Red Herring: Pre-cancerous cells result from a minimum of 4 specific genetic mutations that cause a loss of growth control. Because these cells are rapidly dividing, their telomeres soon become short and they will die. But if a further mutation occurs that permanently activates telomerase, the cell will become immortal and fully cancerous. • This relationship of telomerase to cancer has caused some biologists to fear telomerase activators. But telomerase is not an oncogene, it simply is a mechanism to allow cells to live longer. That is exactly what is required if a person wants to extend their lifespan. The vast majority of our 10 trillion cells are healthy and never lose growth control. Obviously to increase lifespan, our healthy cells have to live longer.
  • 22. Safety • 5 years of development and safety testing before introducing TA-65 • Hundreds of clients taking TA-65 • Some for as long as 3 years • Not a single adverse reaction reported by our licensed physicians • Not a single diagnosis of new cancer • Not a single report of increased cancer load for clients who already had cancer
  • 24. People currently taking TA-65 have seen the following results* • 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) • Improved Immune system: In particular the % and absolute number of senescent CD8+/28- cells has significantly decreased. This is a reversal of what normally happens with age • Improved bone density • Improved cardiovascular and hormonal biomarkers that normally show decline with age • There are also anecdotal results, such as improved energy and athletic performance, but these effects are not universal and vary among individuals *Human trial results substantiating these claims to be published in a peer reviewed scientific journal
  • 25. TA-65 The Only Proven Telomerase Activating Product! Available through licensed doctors Thanks to: Calvin Harley Bill Andrews Woody Wright Maria Blasco for their contributions to Telomere Biology and this presentation

Editor's Notes

  1. I am not a scientist or a doctor. I am a businessman. But some of the best scientists in the world such as Dr. Calvin Harley are advising us. I got interested in telomere biology when I turned 50 and started to notice the ugly ravages of age peeking around the corner. I wanted to do something to save my own ass. That was 14 years ago and since then I have personally worked with no salary and invested millions of dollars to bring our telomerase activating product,TA-65 to market. My personal goal is to play a significant role in the battle to “cure aging.”
  2. 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 don’t divide after birth, but sperm are continually generated so they have telomerase turned on all the time and their telomeres never get short. In fact, older men have slightly longer telomeres than young 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 ordinarysomatic 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 DNA at the tips of our chromosomes that forms telomeres.
  3. Here are a couple examples from the scientific literature:
  4. Do what your doctor says: Eat well, exercise, avoid stress, don’t smoke, and so on.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, our product TA-65.
  5. 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 comes in 25mg capsules. TA-65 transiently turns on the hTERT gene and activates telomerase.
  6. The TA-65 molecule comes from the Astragalus plant that has been in the food chain for over 1,000 years. Because TA-65 is a nutraceutical, it does not need to go through the FDA. We don’t have to wait another decade or more before people can do something about short telomeres.Aging and resulting frailty has been thrust on us by nature without our consent. The resulting decline of vitality and suffering is one of the more tragic aspects of the human condition. I am proud to have an opportunity to do something positive about it.
  7. Gene therapy depicted
  8. The data from current TA-65 users has been evaluated scientifically by Calvin Harley, PhD. and clinically by Joseph Raffaele, M.D.
  9. These graphs show some of the results of a double blind, placebo controlled study we did in 2005. This pivotal study is what prompted us to settle on the specific TA-65 molecule. I should mention that our license from Geron gives us rights to ALL their Telomerase Activators and we could have chosen any other molecule they were working on. TA-65 is in no way a second rate activator.
  10. Who takes: All our clients are informed about Telomere Biology. We do no advertising and make no unsubstantiated claims. Who should take: In general, the shorter one’s telomeres, the more they are likely to benefit from TA-65
  11. 2 cancer questions:If a person has cancer, will TA cause the cancer to grow faster? NO. Cancer cells are immortal with the Telomerase gene (TERT) turned on full blast permanently. A transient activator like TA-65 would have absolutely no effect on a fully cancerous cell. You can’t make something immortal more immortal than it already is.Short telomeres cause double strand breaks and end-to--end fusion of chromosomes which in turn cause mutations and cancer. Remember “Short Telomeres are the Kiss of Death.”
  12. Now I want to play a short clip from a presentation made by Dr. Bill Andrews, a noted Telomere Biologist who is the co-discoverer of the telomerase gene.
  13. Thank you Bill. And by the way Bill deserves a special thanks. He was the first 3rd party scientist to recognize the importance of TA-65 and to independently verify that TA-65 actually works as a telomerase activator. And he was the first paying customer to go on TA-65. There is one thing he said that I want to comment on. Bill said that TA-65 only turns on telomerase “a little.” This is exactly what we want to do. In cancer cells, the telomerase gene is turned on full blast and turned on permanently. That makes the cell immortal. TA-65 turns it on transiently; when you stop taking it, the gene shuts off again. We do not immortalize cells and we don’t want to. The earlier slides show conclusive evidence that TA-65 is a telomerase activator and they also show the reasoning behind why we think it is safe. The next slide shows some of the results from our clients who have taken TA-65 for a year or longer.
  14. Notice that TA-65 has a number of significant effects that cross over between different organ systems. This is not surprising because the method of action is universal. In theory a telomerase activator should be beneficial to each and every cell it gets into.
  15. Thank you. Any Questions?