telomeres: the real biologic clock

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Unlocking the Secrets Of the Telomere Dr. Al Sears, MD The First Step to Reverse Aging

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Learning and understanding the correlation between telomere shortening and disease is the most important principal to stop the aging process. Dr Sears is one of the worlds most respected and renown Anti-Aging physicians in the world. Please visit our website at www.alsearsmd.com or www.searwellnesscenter.com for tons of great free information.

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Page 1: Telomeres: The Real Biologic Clock

Unlocking the Secrets

Of the Telomere

Dr. Al Sears, MD

The First Step to Reverse Aging

Page 2: Telomeres: The Real Biologic Clock

“Harnessing the telomere is the MOST important

event in the history of anti-aging

medicine”

Page 3: Telomeres: The Real Biologic Clock

True“Age-Reversing Therapy”

• My own theory.

• The link between telomeres and aging.

• Shortened telomeres and age-related loss.

Page 4: Telomeres: The Real Biologic Clock

The “Tipping Point” that Will Change

Life on This Planet Forever

• 30 years ago, no one understood HOW or WHY we age... Most believed that we never would.

• As the field of Gerontology advanced, so did the number of theories.

• In light of telomere biology, we realize the so called “causes” of aging were really the “consequences” of aging.

Page 5: Telomeres: The Real Biologic Clock

Theories on Why We Age:

Disposable Soma Theory – We just temporarily house our Genes. Oxidative Stress Theory – Free radicals cause damage to cells. Vital Substance Theory – A vital substance is limiting. Genetic Mutation Theory – Accumulation of mutations cause

aging. Reproductive Exhaustion Theory – After reproduction we die

rapidly. Aging by Design Theory – Aging is programmed. Mitochondrial Dysfunction Theory – Mitochondria become

altered. The Neuroendrocrine Theory – Changes in hormone regulation. Wear and Tear Theory – Self explanatory The Rate of Living Theory – Similar to the Vital Substance

Theory The Waste Product Accumulation Theory – Self explanatory The Cross-Linking Theory – Proteins such as collagen crosslink. The Immune System Theory – Decreased immune function. Errors and Repairs Theory – Inaccurate repair of damage. The Order to Disorder Theory – Decreased maintenance of order. Telomere Theory of Aging – Telomere length controls aging.

Page 6: Telomeres: The Real Biologic Clock

What Really Causes Aging?

Leonard Hayflick

Cell division is a finite biological function and is inexorably tied to the aging process

“Hayflick Limit” describes the number of times a cell can divide

Hayflick was the first to suggest the relationship between cell division and mortality, but did not know the connection to telomeres.

Page 7: Telomeres: The Real Biologic Clock

What are Telomeres?First described in 1975 by Elizabeth Blackburn, who recently earned a Nobel Prize for her discovery.

Telomeres are found at the end of all eukaryotic chromosomes.

Telomeres protect the chromosome from the replication-related loss of genetic info.

Page 8: Telomeres: The Real Biologic Clock

Telomeres

Page 9: Telomeres: The Real Biologic Clock

How Do We Know?From “Hayflick’s Limit,” we know that human cell lines have a “built-in mortality.” That means there’s an internal “authority” that sets the limit on cell division and shuts down the cell line causing death when the limit is reached.

Today we know that mechanism is the telomere.

Once we understood the role of the telomere, the next observation revealed younger cells have longer telomeres, and older cells have shorter telomeres.

Page 10: Telomeres: The Real Biologic Clock

Young Cells Have Long Telomeres...

Old Cells Have Short Telomeres

Two Studies Published in the Journal “Nature” in 1990 Provided Strong Evidence:

Telomeres get shorter with age, with losses ranging from between 30 and 150 nucleotide pairs per replication, depending on cell type.

Cell division/telomere shortening continues until a critical telomere length is reached, at which point the cell is forced into senescence (death) and can no longer replicate.

Cell death prevents replication of incomplete or damaged DNA.

Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

Vaziri H, Schachter F, Uchida I, Wei L, Zhu X, Effros R, Cohen D, Harley CB (1993) Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet 52:661–667

Page 11: Telomeres: The Real Biologic Clock

Can You Make a Cell Older By Shortening Its Telomeres?

The next step was to see what would happen if you took a young cell with long telomeres and artificially shortened them.

If you could make a cell age faster than normal by shortening its telomeres, that would be the next link in proving the “age” of the cell is dependent on the length of the telomere.

And that’s exactly what happened.

Page 12: Telomeres: The Real Biologic Clock

Artificial Shortening the LongTelomeres of Young Cells ACCELERATES

Aging

Page 13: Telomeres: The Real Biologic Clock

Artificially Shortening the LongTelomeres of Young Cells ACCELERATES

Aging

In a groundbreaking study, researchers discovered that when they shortened the telomeres of young, healthy mice, they triggered a host of problems we associated with old age.

In short, by making their telomeres shorter and therefore “dysfunctional,” they were able to artificially create signs of aging. And they made these changes to mice who were otherwise enjoying the vitality of youth.

So then we knew there was some causal relationship.

There’s a cause and effect between short telomeres and aging that we can prove. In addition, we found that we can create the signs of aging simply by shortening the telomere artificially.

Page 14: Telomeres: The Real Biologic Clock

Telomeres Tell Cells How Old They Are

Telomeric mediation of gene expression may explain the relationship between telomere length and aging.

Cells with longer telomeres behave like younger cells.

Cells with shorter telomeres behave like older cells.

Page 15: Telomeres: The Real Biologic Clock

Diseases Affected By Telomere Shortening

• Cardiovascular• Cancer• COPD• Degenerative Disc

Disease• Alzheimer’s• Osteoarthritis• Rheumatoid Arthritis • Osteoporosis• General Immunity• Skin Aging• Macular Degeneration• Liver Cirrhosis

• Muscular Dystrophy• Cell & Tissue Transplants • AIDS• Progeria• Dyskeratosis Congenita• Idiopathic Pulmonary

Fibrosis• Cri du Chat syndrome • Down’s Syndrome• Fanconi’s Anemia• Tuberous Sclerosis• Werner’s Syndrome• And, Aging Itself???????

Page 16: Telomeres: The Real Biologic Clock

Length of the Telomere as Controlling Mechanism of

Aging

Hundreds of published, peer-reviewed studies show the relationship between telomere length and markers of disease, life span and quality of life.

Page 17: Telomeres: The Real Biologic Clock

Telomere Length and All-Cause Mortality

Telomere length was assessed in 143 healthy men and women >60 years of age

Individuals with the shortest telomeres had significantly decreased survival rates:

3 times greater risk of dying from heart disease8.5 times greater risk of dying from infectious disease

Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003 Feb 1;361(9355):393-5.

Page 18: Telomeres: The Real Biologic Clock

Relationship Between Telomere Length and Age-Related Conditions

* *

*

T/S

rati

o

** = p< .05

Atzmon G, Cho M, Cawthon RM, Budagov T, et al. Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1:1710-7.

Page 19: Telomeres: The Real Biologic Clock

Telomere Length & Dementia

Nurses’ Health Study

62 women, > 70 years of age

Controlled for: age, education, smoking history, cardiovascular

disease, hypertension, cholesterol levels, and diabetes

telomere length below the median:

12-times greater risk of being diagnosed with

dementia

9.6-times greater risk of being diagnosed with mild

cognitive impairment.Grodstein F, van Oijen M, Irizarry MC, Rosas HD, Hyman BT, Growdon JH, De Vivo I. Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health study. PLoS One. 2008 Feb 13;3(2):e1590.

Rela

tive

telo

mere

/sin

gle

gen

e r

ati

o

Page 20: Telomeres: The Real Biologic Clock

Telomere Length & Cardiovascular Disease

674 Caucasian males

Measured mean telomere repeat copy number to single gene copy number (T/S ratio)

Found that decreased T/S ratio was significantly associated with risk of MI

log

e-t

ran

sform

ed

T/S

rati

os

Zee RY, Michaud SE, Germer S, Ridker PM. Association of shorter mean telomere length with risk of incident myocardial infarction: a prospective, nested case-control approach. Clin Chim Acta. 2009 May;403(1-2):139-41.

M/I No M/I

Page 21: Telomeres: The Real Biologic Clock

Telomere Length: A Crucial Indicator of Health and

Longevity

Telomere length is:

A marker for cell age

A predictor of longevity

A predictor of age-related disease

Page 22: Telomeres: The Real Biologic Clock

How Do We Slow the Loss of the Telomere?

Factors that accelerate telomere shorteningHomocysteineInflammationOxidationDepressionEmotional StressPhysical Trauma

Factors that slow telomere shortening

Telomerase activators

Page 23: Telomeres: The Real Biologic Clock

Stop Accelerated Telomere Loss by Lowering

Homocysteine

Multiple studies have shown that elevated homocysteine is associated with short telomeres.

In one study, elevated homocysteine tripled the rate of shortening.Bull CF, O'Callaghan NJ, Mayrhofer G, Fenech MF. Telomere length in lymphocytes of older South Australian men may be inversely associated with plasma homocysteine. Rejuvenation Res. 2009 Oct;12(5):341-9.

Richards JB, Valdes AM, Gardner JP, Kato BS, et al. Homocysteine levels and leukocyte telomere length. Atherosclerosis. 2008 Oct;200(2):271-7.

Page 24: Telomeres: The Real Biologic Clock

Nutrient Protocol for Lowering Homocysteine

Vitamin B12: 500 mcg

Folic Acid: 800 mcg

Vitamin B6: 25 mg

Riboflavin (B2): 25 mg

Trimethylglycine (TMG): 500 mg

Page 25: Telomeres: The Real Biologic Clock

Preservation of Telomeres with Vitamin C: In Vitro Evidence

• In 1998, researchers at the Hiroshima Prefectural University in Japan added Vitamin C in the form of Asc-2-O-phosphate (Asc2P) to human vascular endothelial cells.

• They measured a slowdown of age-dependent telomere shortening of 52-62%.

• Telomerase activity underwent an age-dependent decline which was significantly slowed by Asc2P.

• Researchers concluded that age-dependent telomere-shortening was decelerated by both suppression of intracellular oxidative stress and by telomerase retention

Furumoto K, Inoue E, Nagao N, Hiyama E, Miwa N. Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress. Life Sci. 1998;63(11):935-48.

Page 26: Telomeres: The Real Biologic Clock

Preserve Telomere Length with Vitamin C:

In Vivo Evidence

Vitamin levels were assessed in 586 women aged 35-74

Analysis controlled for age, overall health, BMI, smoking, stress level, cardiovascular disease, and diabetes.

Women in the 4th quartile of vitamin C intake had significantly longer telomeres relative to women in the 1st quartile.

1st Quartile 4th Quartile

Mean

Telo

mere

Len

gth

(B

P)

Xu Q, Parks CG, DeRoo LA, Cawthon RM, Sandler DP, Chen H. Multivitamin use and telomere length in women. Am J Clin Nutr. 2009 Jun;89(6):1857-63.

Page 27: Telomeres: The Real Biologic Clock

Stress in the Workplace Causes

Shortening of the Telomere

1st Quartile 4th Quartile

Damjanovic, et al., J Immunol. 2007 Sep 15;179(6):4249-54

Page 28: Telomeres: The Real Biologic Clock

Depression Causes Shortening of the

Telomere

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

Page 29: Telomeres: The Real Biologic Clock

Reducing Stress Slows the

Loss of the TelomereChronic stress has been shown to accelerate telomere shortening.

After adjusting for age and various health/behavioral factors, women with the highest stress levels had the shortest telomeres.

The degree of telomere shortening correlated to a minimum of a full decade of again

Ave

rag

e T

/S

Rati

o

High Stress Low Stress

Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5.

Page 30: Telomeres: The Real Biologic Clock

Superoxide Dismutase (SOD)

Slows Telomere Shortening

Superoxide dismutase is a naturally occurring cellular antioxidant that aids the immune system cells in killing or deactivating invading microorganisms.

In human fibroblasts with low antioxidant capacity, increasing cellular superoxide dismutase activity slowed telomere shortening and increased the life span of the cells.

Serra V, von Zglinicki T, Lorenz M, Saretzki G. Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J Biol Chem. 2003 Feb 28;278(9):6824-30.

Page 31: Telomeres: The Real Biologic Clock

Maintain Telomere Length with Omega-3

Fatty Acids

Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA. 2010 Jan 20;303(3):250-7.

Page 32: Telomeres: The Real Biologic Clock

The Right Exercise Increases

Telomerase Activity

Murine modelVoluntary running for 3 weeks induced:

A 2.9-fold increase in aortic telomerase activity A 3.3-fold increase in telomerase activity in circulating mononuclear cells in the spleen

Human model Compared to controls, pro athletes exhibited:

2.5-fold increase in telomerase activity in young athletes1.8-fold increase in telomerase activity in middle-agedWerner C, Fürster T, Widmann T, Pöss J, et al. Physical exercise prevents cellular senescence in

circulating leukocytes and in the vessel wall. Circulation. 2009 Dec 15;120(24):2438-47.

Page 33: Telomeres: The Real Biologic Clock

Keeping Telomeres Long

Right Exercise

Anti-Oxidants Omega 3’s Vitamin D3 Don’t Smoke

Weight Management

Reduce Stress Reduce Depression Reduce Pessimism Be Happy!

Page 34: Telomeres: The Real Biologic Clock

The History-Making Story of Telomerase

Telomerase is the enzyme responsible for re-building telomeres.

Telomerase activity is observed in fetal tissue, adult germ cells, and tumor cells.

Telomerase is “turned off” in all other cells.

Page 35: Telomeres: The Real Biologic Clock

Activation of Telomerase Has Been Shown To:

1. Immortalize cells

2. Reverse the age of tissue

3. Reverse aging in whole organisms

Page 36: Telomeres: The Real Biologic Clock

Telomerase Can “Immortalize” Cells

Study published in the journal Science:

Human cells were encoded with the human telomerase gene (hTERT).

Control cells showed telomere shortening, as well a marker of cell death.

Telomerase+ cells had longer telomeres.

By the time the study was published, the telomerase+ cells had exceeded their expected lifespan by 20+

replications.

Bodnar AG, Ouellette M, Frolkis M, Holt SE, et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998 Jan 16;279(5349):349-52.

Page 37: Telomeres: The Real Biologic Clock

Telomerase Restores Youthful Markers in Live Tissue

Normal human dermal fibroblasts were transfected with hTERT and then grafted onto mouse skin.

Mice grafted with telomerase-negative control cells exhibited phenotypic signs of senescence (increased fragility, reduced levels of collagen I and III, and subepidermal blistering).

Mice grafted with telomerase+ cells exhibited a youthful phenotype, despite the same number of replications.

Funk WD, Wang CK, Shelton DN, Harley CB, Pagon GD, Hoeffler WK. Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model. Exp Cell Res. 2000 Aug 1;258(2):270-8.

Page 38: Telomeres: The Real Biologic Clock

“The results were strikingly unequivocal. The telomeres in cells with hTRT lengthened, and

the cells themselves kept on multiplying, through the Hayflick limit and well

beyond.

At the time the papers were submitted they had made 20 or more extra divisions, yet they looked young, vigorous and essentially norma

l.”

Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998 Jan 16;279(5349):349-52.

Page 39: Telomeres: The Real Biologic Clock

Can You REVERSE the Signs of Aging by Artificially Lengthening

the Telomere?

Markers in Live TissueAfter establishing:

Young cells have long telomeres and old cells have short telomeres; And proving you can accelerate the signs of aging by artificially shortening the telomere...

The next step was showing that if we turn on the telomerase, the enzyme that REBUILDS the telomere, we can slow the shortening of telomeres in a cell. And in some cases make them longer.

If the theory help up, that would mean you could actually REVERSE the signs of aging by artificially lengthening the telomere.

And that’s what happened during a recent Harvard study.

Page 40: Telomeres: The Real Biologic Clock

Harvard Researchers Demonstrate How Telomerase can Reverse

Aging In a Whole Organism

Page 41: Telomeres: The Real Biologic Clock

Harvard Researchers Demonstrate How Telomerase can Reverse

Aging In a Whole Organism

Page 42: Telomeres: The Real Biologic Clock

A Groundbreaking Study...

Harvard Medical School Professor, Ronald DePinho, used the TERT-ER mouse to demonstrate the profound effect of telomerase activation on age management.

TERT-ER mice have short dysfunctional telomeres and are deficient in telomerase.

4-hydroxytamoxifen (4-OTH) is used to induce telomerase in TERT-ER mice.

Jaskelioff M, Muller FL, Paik JH, Thomas E, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2010 Nov 28

Page 43: Telomeres: The Real Biologic Clock

Mice with Short Telomeres

Were Aged and Atrophied

Decreased survivalTERT-ER mice: 43.5 versus

Telomere-intact mice: 86.8 weeks

Widespread tissue atrophyDecreased brain weight/hypomyelination

Testicular atrophy/decreased testicular sizeSplenic atrophy

Intestinal crypt depletion/villous atrophy

Decreased fertility

Decreased olfactory discrimination (common aging marker in mice)

Page 44: Telomeres: The Real Biologic Clock
Page 45: Telomeres: The Real Biologic Clock

Aging Brain Restored to Normal Size

Reversed cerebral atrophy

Reversed hypomyelination

Restored white matter structures

Elongated telomeres in the corpus callosum

Neural progenitor cells were reactivated

TERT-ERTelomerase activated

Bra

in w

eig

ht

(mg

)

P=0.02

Page 46: Telomeres: The Real Biologic Clock

Testicular Atrophy is Reversed and Fertility is Restored

P=0.0001

TERT-ER Telomerase activated

Test

es

weig

ht

(g)

Page 47: Telomeres: The Real Biologic Clock

Other Organs Were Also Restored

Similar results were seen in the spleen and the intestines.

Performance on olfactory discrimination tasks was restored to youthful levels.

“When we flipped the telomerase switch on and looked a month later, the brains had largely returned to normal.”

-- Dr. Ronald DePinho commenting on his groundbreaking Harvard study

Page 48: Telomeres: The Real Biologic Clock
Page 49: Telomeres: The Real Biologic Clock

Telomerase Activity Predicts Longevity in Humans

Multi-generational study of Ashkenazi Jews with exceptional longevity

Parent group (n = 86; average age of 97 years)Offspring group (n = 175)

Control group (n = 93)

Found that the population exhibited abnormally high telomerase activity, mediated by a mutation of hTERT – a catalytic subunit of telomerase.

Results link human longevity with telomerase activity

Atzmon G, Cho M, Cawthon RM, Budagov T, et al. Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1:1710-7.

Page 50: Telomeres: The Real Biologic Clock

Telomerase Activity Has Positive Impact On Adult Stem Cells

“The real targets for [Telomerase Activators] are the adult stem cells scattered throughout our body, which

are required for regenerating and repairing our organs and tissues.

Activating telomerase in populations of adult stem cells can extend their function and help promote

organ repair and regeneration.”

--Bryant Villeponteau, PhD. [ex-Geron Corporation, ex-Sierra Sciences] on-line post to Dr. Stephen Coles and the Gerontology Research Group 1/16/11

Page 51: Telomeres: The Real Biologic Clock

Telomerase Activity Has Positive Impact On Adult Stem Cells

“The real targets for [Telomerase Activators] are the adult stem cells scattered throughout our body, which

are required for regenerating and repairing our organs and tissues.

Activating telomerase in populations of adult stem cells can extend their function and help promote

organ repair and regeneration.”

--Bryant Villeponteau, PhD. [ex-Geron Corporation, ex-Sierra Sciences] on-line post to Dr. Stephen Coles and the Gerontology Research Group 1/16/11

Page 52: Telomeres: The Real Biologic Clock
Page 53: Telomeres: The Real Biologic Clock

How to Activate Telomerase Now...

Page 54: Telomeres: The Real Biologic Clock

Assessment of Telomere Length

Repeat Diagnostics: First and only CLIA Certified laboratory in the world to provide cell type specific telomere length measurements. www.repeatdiagnostics.com

Spectracell: Uses “whole blood” sample. Does not differentiate between lymphocytes and granulocytes. www.spectracell.com

Life Length: Founded by Dr. Maria Blasco, Director of the Spanish National Cancer Institute. First to measure percentage of critically short telomeres. www.lifelength.com

Page 55: Telomeres: The Real Biologic Clock

The Search for the First Telomerase Activator

Back in the early 1990s, an entrepreneur named Michael West heard about the amazing breakthroughs in telomere biology at an anti-aging conference.

Convinced of its effectiveness and place in history, Michael started the Geron Corporation with the vision of bringing the first commercially available telomerase activator to the public.

Page 56: Telomeres: The Real Biologic Clock

Geron Corporation

Discovered a process to extract a very rare molecule that is found in tiny amounts in the Chinese herb Astragalus and they named the molecule TA-65.

Patented the sequence of the telomerase genome and granted license to TA-Sciences to sell TA-65.

Dr. Bill Andrews: As Director of Molecular Biology at the Geron Corporation from 1992 to 1997 was one of the principal discoverers of the components of human telomerase. 

Page 57: Telomeres: The Real Biologic Clock

Telomerase Activation: TA-65®

TA-65®

Naturally-occurring, highly purified single molecule derived from the Chinese herb Astragalus

Activates the hTERT gene

In vitro: moderately activated telomerase in keratinocytes, fibroblasts, and immune cells

In vivo: orally administered in doses of 10-50 mg/day for 12-months

Harley CB, Liu W, Blasco M, Vera E, Andrews WH, Briggs LA, Raffaele JM. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011 Feb;14(1):45-56.

Astragalus tragacantha (ssp. Vicentinus)

Kingdom: Plantae Division: Magnoliophyta Class: Magnoliopsida Order: Fabales Family: Fabaceae Subfamily: Faboideae Tribe: Galegeae Genus: Astragalus

Page 58: Telomeres: The Real Biologic Clock

Results of TA-65®

Following 1-year on TA-65 ®, we observed a significant decrease in the percent of critically-short telomeres.

Page 59: Telomeres: The Real Biologic Clock

TA-65® Reduces Number of Damaged Immune

Cells

A study published in the September 7, 2010 issue of the journal Rejuvenation Research, showed TA-65 significantly reduced...

Senescent cytotoxic T cells and natural killer cells...

With a significant reduction in the number of cells with short telomeres (<4 kbp; p = 0.037).

Harley, C., Weimin L., et al, “A Natural Product Telomerase Activator As Part of a Health Maintenance Program,” Rejuvenation Research 2010

Page 60: Telomeres: The Real Biologic Clock

By Activating TelomeraseTA-65® Produces Younger

Cells

Researchers at TA Sciences tested a group of people and measured the number of white blood cells that looked old, and the number that looked young. Then the people started taking TA-65®.

After three months, they were found to have a ratio of young-looking cells to old-looking cells that someone would have if they were 20 YEARS YOUNGER.

Harley, C., Weimin L., et al, “A Natural Product Telomerase Activator As Part of a Health Maintenance Program,” Rejuvenation Research 2010

Page 61: Telomeres: The Real Biologic Clock

TA-65® in My Own Practice

First doctor licensed to administer TA-65.

53 patients following TA-65 protocol since August 2008.

Page 62: Telomeres: The Real Biologic Clock

You Can Have Your Telomeres Tested

Repeat Diagnostics: First and only CLIA Certified laboratory in the world to provide cell type specific telomere length measurements. www.repeatdiagnostics.com

Spectracell: Uses “whole blood” sample. Does not differentiate between lymphocytes and granulocytes. www.spectracell.com

Life Length: Founded by Dr. Maria Blasco, Director of the Spanish National Cancer Institute. First to measure percentage of critically short telomeres. www.lifelength.com

Page 63: Telomeres: The Real Biologic Clock

Case Study: Michael

Michael recently turned 62 but has the clinically documented “pulmonary age” of a 24-year old.

Michael’s “neurological age,” is only 44, a sign he has the brainpower of a much younger man.

Michael had other remarkable changes including better eyesight, lower cholesterol and dramatically higher testosterone.

Page 64: Telomeres: The Real Biologic Clock

Case Study: Michael

All that extra energy helped him win at the recent North American Grappling Association Championship. In the space of one hour, Michael won two first place titles against men who were twenty years his junior.

In Michael’s own words:

“With TA-65 I lost 20 pounds, increased my muscle mass and flexibility, eliminated joint pain I’ve had for years and miraculously made the inside of my body younger.”

Page 65: Telomeres: The Real Biologic Clock

Patient M.F.Patient M.F.Age 58 to 61Age 58 to 61

Baseline 6M 12M 18M 24M 30M

Biological Marker Age 56 52 52 43 51 44

Page 66: Telomeres: The Real Biologic Clock

Patient M.F.Patient M.F.Age 58 to 61Age 58 to 61

Baseline 6M 12M 18M 24M 30M

Age Quotient 103 111 113 137 117 138

Page 67: Telomeres: The Real Biologic Clock

Dr. Sears Age 51

• Initial Telomere Length August 08, 2008

– Mean Telomere Length = 7.65 (kb)

Telomere Biologic Age = 35

Chronologic Age = 51

Age Quotient = 146

Page 68: Telomeres: The Real Biologic Clock
Page 69: Telomeres: The Real Biologic Clock

Dr. Sears Age 56

October 30, 2012 Mean Telomere Length = 8.4 kb

Telomere Biologic Age = 21

Chronologic Age = 56

Age Quotient = 267

Page 70: Telomeres: The Real Biologic Clock

Dr. Sears Age 51 to 56

Baseline Current

Biological Marker Age 35 21

Page 71: Telomeres: The Real Biologic Clock

Dr Sears Results to Date

• Baseline Telomere A/Q = 146• Telomere A/Q October 30, 2012 = 267• Telomere Age Quotient Increased by

83%• Reversed Age-Associated Shortening

of Telomere• An Example of Anti-Aging

Page 72: Telomeres: The Real Biologic Clock

Dr. Sears Age 51 to 56

Baseline Current

Age Quotient 146 267

Page 73: Telomeres: The Real Biologic Clock

New Breakthroughs in Telomerase Activation

New research uncovered at least 123 nutrients, vitamins and other natural compounds that have the ability to “turn on” telomerase in the human genome.

Not only are these nutrients proven effective, they’re more affordable than TA-65.

Today, telomerase therapy is more accessible than ever before.

Page 74: Telomeres: The Real Biologic Clock

Silymarin Boosts Telomerase Activity by

300% This herbal extract is effective for detoxification but was recently discovered to activate telomerase.

Published in the Journal of Cardiovascular Pharmacology, researchers discovered Silymarin:

Increased telomerase activity 3-fold; Reduced the number of senescent cells, and Increased the activity of endothelial progenitor cells by up to 64% Parzonko, Andrzej MSc; Naruszewicz, Marek PhD. Silymarin Inhibits Endothelial Progenitor Cells' Senescence and Protects Against the Antiproliferative Activity of Rapamycin: Preliminary Study. Journal of Cardiovascular Pharmacology: December 2010. Volume 56, Issue 6. pp 610-618

Page 75: Telomeres: The Real Biologic Clock

N-Acetyl Cysteine (NAC)

This potent amino acid is a building block of your body’s primary antioxidant called glutathione (GSH).

Published in the journal Mechanisms of Ageing and Development, researchers discovered NAC turns on the human telomerase gene.

“Chronic exposure to NAC can delay senescence of diseased endothelial cells via hTERT activation and transient telomere

stabilization...”

Guillaume V, et al. Chronic treatment with N-acetyl-cysteine delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients. Mechanisms of Ageing and Development, Volume 129, Issue 5, May 2008, Pages 261–270.

Page 76: Telomeres: The Real Biologic Clock

Gamma Tocotrienol

One of the four lesser-known forms of vitamin E, gamma tocotrienol can, “modulate the length of the telomere possibly via telomerase.”

From their study published in Oxidative Medicine and Cellular Longevity, the researchers concluded that after being exposed to gamma tocotrienol for just 24 hours...

“...telomere lengths of treated cells appear to have been roughly 16% longer than controls after only this very short

period of exposure.”

Suzana Makpol, et al. Gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals. Oxidative Medicine and Cellular Longevity, 3(1); Jan-Feb 2010.

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Resveratrol

By activating telomerase, this well-known anti-aging nutrient from red wine increases the number of endothelial progenitor cells. These vital cells make repairs to damaged blood vessels.

According to the lead researcher from the study published in the British Journal of Pharmacology:

“Resveratrol significantly increased telomerase activity...”

Xia, L. Wang XX, et al. Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol. 2008 October; 155(3): 387–394.

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Green Tea Extract (EGCG)

The extract of green tea, EGCG, has a powerful effect on telomeres.

In a study published in the British Journal of Nutrition, the telomeres of green tea drinkers were about 0.46 kilobases longer.

This average difference in the telomere length corresponds to, “approximately a difference of five years of life.”

Chjan R, Woo J, Suen E, Leung, Tang N. Chinese tea consumption is associated with longer telomere length in elderly Chinese men. Br. J Nutr. 2010 Jan;103(1):107-13. Epub 2009 Aug 12. 

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Ginkgo Biloba Extract

Originally known as a brain booster because it helps open up blood vessels, there’s new evidence from a study published in the Journal of Cardiovascular Pharmacology that:

“...ginkgo biloba extract significantly increased telomerase activity...”

Ginkgo helps prevent the loss of the telomere by activating telomerase in the sensitive cells that line your blood vessels known as the endothelium. Dong, X, et al. Ginkgo Biloba reduces endothelial progenitor cell senescence through augmentation of Telomerase activity. Journal of Cardiovascular Pharmacology. Feb 2007, vol.49, issue 2, pp. 111-115.

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Vitamin D3 and Folic AcidFamous for it’s ability to increase immune function and prevent cancer, vitamin D also activates telomerase.

One very recent study from the International Journal of Obesity showed vitamin D increased telomerase activity by 19.2%.

Folic acid is one of the B vitamins I prescribe to help stop the loss of your telomeres. And it’s one of five nutrients used to get rid of excess homocysteine that builds up in your blood stream when you’re antioxidant levels start to drop.

A study from the Journal of Nutrition suggests folic acid stimulates the activation of telomerase.

Zhu H, Guo D, Li K, Pedersen-White J, Stallmann-Jorgensen IS, Huang Y, Parikh S, Liu K, Dong Y. Increased telomerase activity and vitamin D supplementation in overweight African Americans. Int J Obes (Lond). 2012 Jun;36(6):805-9.

Paul L, et al. Telomere length in peripheral blood mononuclear cells is associated with folate status in men. J Nutr. 2009 Jul;139(7):1273-8.

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Dr. Al Sears, MD

Wellness Research Foundation 11903 Southern Blvd., Ste. 208

Royal Palm Beach, FL 33411 866-792-1035

www.alsearsmd.com