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

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 Cellsgenerally 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 10,000base 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 ofcells 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. Slide courtesy of Woody Wright, Ph.D. Telomerase Extends Cell Life Span and Overcomes the Hayflick Limit 160 ] hTERT + Cells have Telomerase 140 120 100 Population Doublings ] hTERT - Cells have No Telomerase 80 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-65Work? 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. 10,000 genes on a chip Schematic of cell rejuvenation using hTERT: Gene Expression Comparison: Actual data in: Funk et al, Exp Cell Res, 2000 Telomerized (rejuvenated to “Young”) Young Old (notice overall changes)

14. Is TA-65the “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 • Reduced Spleen Size • Decreased Wound Healing • Decreased Lifespan! These Mice are the 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. Human skin on a mouse Old Telomerized Skin Reconstitution: Old Cells Become Young Young Slide courtesy of Bill Andrews Funk et al, Exp Cell Res, 2000

18. Broad Potential for Tissue System Regeneration Immune cells – memory and naïveHematopoietic stem cellsLung alveolar cells Skin – dermis,  epidermis, vasculatureVascular intima (endothelium)Osteoblasts, MSCsGI track epithelial cells Liver – hepatocytesRetinal pigmented tissue of eyeChondrocytesSkeletal muscleKidney – 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

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

23. Verified by Independent research

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-65The 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