A4M Conference Presentation for Life Length, 12-13-13 Old Age = Telomerase Enzyme Deficiency Syndrome (TEDS)

3. ABC News
Diane Sawyer

5. Do We Have
to Age?

8. Human Reproductive Cells

9. Founder, President & CEO
Sierra Sciences
Reno, Nevada
William H. Andrews, Ph.D.

10. William H. Andrews, Ph.D.
32 Years in Biotech Research
45 U.S. Issued Patents
2nd Place United States Inventor of the Year

11. Telomere
Shortening
Disease

12. Bad Things
Happen When
Telomeres
Get Short!
Telomere

19. Sierra Sciences, LLC

23. Sierra Sciences, LLC

24. Congratulations
Elizabeth Blackburn, Carol Greider, and Jack Szostak
2009 Nobel Prize in Medicine!

25. United States Inventor of the Year
(Second Place)

26. Popular Science – August 2011

27. NBC Today Show

28. Men’s Journal
Magazine
August 2013

31. HBO Documentary
“Long For This World”
First Quarter 2014

32. September 2-8
is
Telomere
Research
Week

33. Some People are Born with Short
Telomeres

34. Progeria
Mech Ageing Dev. 2009 Jun;130(6):377-83. Epub 2009 Mar 20.
Short Telomere
Disease

35. Progeria
Mech Ageing Dev. 2009 Jun;130(6):377-83. Epub 2009 Mar 20.
Short Telomere
Disease
Life Expectancy - 20 Years

36. Progeria
Mech Ageing Dev. 2009 Jun;130(6):377-83. Epub 2009 Mar 20.
Short Telomere
Disease
Life Expectancy - 20 Years
Preventing Telomere Shortening
Could Cure These Kids!

37. Bad Things
Happen When
Telomeres
Get Short!

38. Telomere Length Affects
Almost Everything
• Cancer
• Immune
Senescence
• AIDS
• Alzheimer’s
• Osteoporosis
• Stem Cells
• Skin Care
• Pets
• Medical Research
• Aging

39. Telomere Length Affects
Almost Everything
• Cancer
• Immune
Senescence
• AIDS
• Alzheimer’s
• Osteoporosis
• Stem Cells
• Skin Care
• Pets
• Medical Research
• Aging

40. Short Telomeres in Normal
Breast Cells

41. Telomere Length Affects
Almost Everything
• Cancer
• Immune
Senescence
• AIDS
• Alzheimer’s
• Osteoporosis
• Stem Cells
• Skin Care
• Pets
• Medical Research
• Aging

42. Telomere Length Affects
Almost Everything
• Cancer
• Immune
Senescence
• AIDS
• Alzheimer’s
• Osteoporosis
• Stem Cells
• Skin Care
• Pets
• Medical Research
• Aging

43. Telomere Length Affects
Almost Everything
• Cancer
• Immune
Senescence
• AIDS
• Alzheimer’s
• Osteoporosis
• Stem Cells
• Skin Care
• Pets
• Medical Research
• Aging

45. Fick LJ, et al., Cell Rep. 2012 Dec 27;2(6):1530-6
P < 0.0001

46. What Can Be
Done About
Telomere
Shortening?

47. Managing Telomere Length
1. Know the length of your telomeres

48. Telomeres Shorten as Cells Divide
Hastings, et al. Cell Prolif. 37, 317-324 (2004)

49. Telomeres Shorten with Age
Tsuji, et al., Forensic Sci Int 2002

50. Okuda, K., et al., Atherosclerosis, 2000
Telomeres Shorten with Age

51. Average Telomere Lengths
versus
Percent of Short Telomeres
?

52. How Does Telomere Shortening
Cause Bad Things?

54. Fold Back Model

55. Adapted From Essential Cell Biology – Bruce Alberts - 1998
Promoter
(or TATA Box) Gene ->Enhancer
A Precedence in Transcription Initiation
Can be >300,000
Bases Away

56. TRF(1/2)-hRAP1
TRF(1/2)-hRAP1
Telomere
Adapted From Essential Cell Biology – Bruce Alberts - 1998

57. Telomere Length Measurement
1. Terminal Restriction Fragment (TRF)
2. Q-PCR
3. Fluorescence In Situ Hybridization (FISH)
4. Flow FISH
5. HT Q-FISH
6. Universal STELA

58. Telomere Length Measurement
1. Terminal Restriction Fragment (TRF)
2. Q-PCR
3. Fluorescence In Situ Hybridization (FISH)
4. Flow FISH
5. HT Q-FISH
6. Universal STELA
Short
Telomeres

59. Telomere Length Measurement
1. Terminal Restriction Fragment (TRF)
2. Q-PCR – Commercially available
3. Fluorescence In Situ Hybridization (FISH)
4. Flow FISH – Commercially available
5. HT Q-FISH – Commercially available
6. Universal STELA

60. Managing Telomere Length
1. Know the length of your telomeres
2. Decrease the rate of telomere shortening

61. Tug of War
Shorteners Lengtheners

62. Shorteners Only

68. Basal Level
Telomere
Shortening

69. Increase Number of Shorteners

71. Accelerated
Telomere
Shortening

72. Preventing Accelerated Telomere
Shortening

73. Accelerated Shortening

74. Decrease Number of Shorteners

75. Exercise

76. German National Track and Field Team
Werner, et al., Circulation. 2009 Dec 15;120(24):2438-47
p < 0.001

77. German National Track and Field Team
p < 0.001
Werner, et al., Circulation. 2009 Dec 15;120(24):2438-47

78. Vigorous Aerobic Exercise
LaRocca, et al., Mech Ageing Dev. 2010 Feb;131(2):165-7.

79. Physical Activity in Leisure Time
Cherkas, et al., Arch Intern Med. 2008 Jan 28;168(2):154-8.

80. August
2013

81. Stress

82. Stress
p = 0.05
Damjanovic, et al., J Immunol. 2007 Sep 15;179(6):4249-54

83. Stress
Epel, et al., Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5.

84. Stress
Tyrka, et al., Biol Psychiatry. 2010 Mar 5. [Epub ahead of print]

85. Depression

86. Mood Disorders
Simon, et al., Biol Psychiatry. 2006 Sep 1;60(5):432-5.

87. Obesity, Diet,
Antioxidants, &
Smoking

88. 2284 women from the Nurses’ Health Study
Cassidy, et al., Am J Clin Nutr. 2010 Mar 10. [Epub ahead of print]

89. Valdes, et al., Lancet. 2005 Aug 20-26;366(9486):662-4.
p = 0.031 p = 0.019
p = 0.017 p = 0.045
Obesity
Smoking

90. Smoking
p = .001
Morlá, et al., Eur Respir J. 2006 Mar;27(3):525-8.

91. Omega 3 Fatty Acids

92. Omega 3 Fatty Acids
Farzaneh-Far, et al., JAMA. 2010 Jan 20;303(3):250-7.

93. Vitamin D

94. Vitamin D
Richards, et al., Am J Clin Nutr. 2007 Nov;86(5):1420-5.

95. Attitude

96. The MONICA Northern Sweden Study
Self Perceived Aging
Nordfjäll et al., Scand J Public Health. 2008 Sep;36(7):744-52

97. The MONICA Northern Sweden Study
Self Perceived Aging
Nordfjäll et al., Scand J Public Health. 2008 Sep;36(7):744-52

98. The MONICA Northern Sweden Study
Self Perceived Aging
Nordfjäll et al., Scand J Public Health. 2008 Sep;36(7):744-52

99. Pessimism
O’Donovan, et al., Brain Behav Immun. 2009 May;23(4):446-9.

100. Preventing
Accelerated Telomere Shortening
 Exercise
 Anti-Oxidants
 Omega 3’s
 Vitamin D3
 Don’t Smoke
 Don’t be Obese
 Reduce Stress
 Reduce Depression
 Reduce Pessimism
 Be Happy!
These Are Things People Can Do NOW!

101. Accelerated Shortening

102. Decrease Number of Shorteners

103. Basal Level
Telomere
Shortening

104. Managing Telomere Length
1. Know the length of your telomeres
2. Decrease the rate of telomere shortening
3. Increase the length of the telomeres

105. Telomeres Don’t Shorten in
Reproductive Cells!

106. No Shortening

107. Telomerase
Telomere
Telomerase

108. Only Found in Our Reproductive Cells!

111. What Happens if Telomerase is
Produced in All Cells?

112. Sierra Sciences
Reno, Nevada
Founded in 1999

113. Searching for Telomerase
Inducers
That Stop or Reverse Telomere
Shortening in Humans!
Sierra Sciences
Reno, Nevada

115. Focused on Finding Ways to Lengthen Telomeres

116. Reproductive Cells Produce
Telomerase
Telomerase GeneRegulatory
Element

117. The Gene is Repressed in All
Other Cells
Telomerase GeneRegulatory
Element
Repressor

118. Telomerase GeneRegulatory
Element
Discover Telomerase Inducers
Dimmer
Switch

119. 39 Families of Chemicals Identified!
Human Testing Within 3 Years!
Highest in vitro Potency So Far = 16%
100% Within 1 Year.

120. In the Meantime

121. Natural Products Already
on the Market!

122. Decreased Shortening
So Far!

123. Clinical Studies

124. Study #1
Not Published

127. Study #2

128. Telomerase Preferentially
Elongates the Shortest Telomere

129. Ball of Yarn
Telomere

130. Ball of Yarn
Telomere

132. Abundance of Short Telomeres Reduced
(Harley, Liu, Blasco, Andrews, Briggs and Raffaele, Rejuvenation Research,
2010)

133. No Cancer
(Harley, Liu, Blasco, Andrews, Briggs and Raffaele, Rejuvenation Research,
2010)

134. Measure the
Percent of Short
Telomeres

135. Clinical Studies
Underway

136. Study #3

137. Clinical Study
 Faces, Hands, etc., Photographed
 Short telomeres measured
 Waist circumference
 Body Mass Index (BMI)
 Total Body Water (TBW)
 Total Body Fat (TBF)
 Oxidative Stress Panel
 Routine Urinalysis

138. Clinical Study
 CBC w/Diff
 Thyroid panel including a Free T3
 HSCRP (Highly sensitive C Reactive
Protein)
 Total and free Testosterone
 Total Estrogen
 Chem 20 including a lipid profile
 IGF-1

139. Study #4

140. Clinical Study
 Double Blind Placebo Controlled
 Short Telomeres Measured

141. The Future!

142. No Shortening

144. Making Telomeres Longer?

145. Bernardes de Jesus B, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA. EMBO Mol
Med. 2012 Aug;4(8):691-704. Epub 2012 May 15.
Telomerase gene therapy in adult and
old mice delays aging and increases
longevity without increasing cancer.

146. Bernardes de Jesus B, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA. EMBO Mol
Med. 2012 Aug;4(8):691-704. Epub 2012 May 15.
Telomerase gene therapy in adult and
old mice delays aging and increases
longevity without increasing cancer.

149. Reversal of
Short Telomere Disease
in Mice!
 33% Increase in Telomere Lengths
 Restoration of Fertility
 Restoration of Spleen Size
 Restoration of Sense of Smell
 Restoration of Brain Size and Function
 3-Fold Increase in Survival After 25 Weeks.

151. To Learn
More

153. Thank you!

154. Questions?