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

1. Telomerase Activation:
The Key to Unlocking the
Aging Puzzle
Presentation by:
Noel Thomas Patton
Founder and Chairman
Telomerase Activation Sciences, Inc.

2. The Nobel prize in 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 DNA sequences (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 as chromosome 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,
Telomeres get Shorter…

16. …and can no longer 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 of short
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 Cell Life 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 And Reverses
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 striking in 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 treated with 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, not in 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