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

2007 Long

Telomeres

Short

Telomeres

Telomere Biology: The Emerging Paradigm Shift

Presentation by:

Noel Thomas PattonFounder 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 LimitP

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lings

TimeSlide 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 is a molecular motor that adds new DNA onto

the ends of telomeres

hTERT

hTR

template

Telomere

Telomerase

Slide courtesy of Woody Wright, Ph.D.

Telomerase Extends Cell Life Span and Overcomes the Hayflick

Limit

Days

0 50 100 150 200 250 300

hTERT +

hTERT -

40

60

80

100

120

140

160

Pop

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]

Slide courtesy of Woody Wright, Ph.D.

Cells have Telomerase

Cells have No Telomerase

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:

Actual data in: Funk et al, Exp Cell Res, 2000

10,000

genes on

a chip

10,000

genes on

a chip

Young Telomerized

(rejuvenated to “Young”)

Old (notice overall changes )

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

Long Telomeres

Gray and Thinning Hair

Weakened Immune System

Intestinal Atrophy

Reduced Spleen Size

Decreased Wound Healing

Decreased Lifespan!

Rudolph, et al Cell 1999

Samper, et al EMBO rep 2001

These Mice are the

Same Age!

The one on top has no

telomerase.

Slide courtesy of Bill Andrews

Human

skin on

a mouse

YoungYoung TelomerizedTelomerized

Skin Reconstitution: Old Cells Become Young

Slide courtesy of Bill Andrews

Funk et al, Exp Cell Res, 2000

OldOld

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 eye ChondrocytesSkeletal 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

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