Altering the Genetic ClockTelomeres, Telomerase and

Telomerase Activation

Al Sears, MD

Taking the Historic First Step Towards Agelessness…

• Why telomere biology is the best current theory of aging.

• Learn the risk factors that accelerate the shortening of the telomere.

• Learn the simple strategies that slow the loss of the telomere.

• Participate in the historic discovery of telomerase activation.

What are Telomeres?• Telomeres are structures found at the ends of

chromosomes.

• Telomeres protect chromosome ends from recombination, fusion to other chromosomes, or degradation by nucleases.

• They permit cells to distinguish between random DNA breaks and chromosome ends.

• They also play a significant role in determining the number of times that a normal cell can divide.

• Telomeres are extensions of the linear, double-strand DNA and are found at each end of both strands.

• Each chromosome will have four telomeric tips. In humans, the forty-six chromosomes are tipped with ninety-two telomeric ends.

• Telomeres consist of several thousand repeats of the specific nucleotide sequence TTAGGG.

• It was originally believed that normal cells had the potential to divide and function indefinitely.

• That belief led scientists to think that aging was not the result of events that occurred within normal cells.

• Aging was thought to be the result of extracellular events such as radiation or wear and tear from the environment.

• Aging is a genetically initiated series of events with the telomere serving as the central control.

The Hayflick Limit:• In 1961 Leonard Hayflick and Paul

Moorhead discovered that normal human somatic cells have a finite number of replicative cycles and a built-in counting mechanism. Today this phenomenon is known as the Hayflick Limit.

• Hayflick concluded that the counting mechanism was located in the cells nucleus and that telomeres were involved.

• At the time telomere function was unknown, although it was believed that they might have a role as a stabilizing structure.

• Knowing the TTAGGG sequence, Hayflick and his colleagues were then able to determine that telomeres became shorter each time a normal cell divided until a critical length was reached.

• When the length was reached the cell stopped dividing.

• Hayflick interpreted his findings to mean that the limited replicative (in vitro) capacity of cultured normal cells was a sign of their aging and longevity. He also concluded that immortal cultured cells are mostly cancer cells.

Need proof that shortening = aging

Need evidence for disease and telo shortening

Telomeres and Aging:• Contrary to a century of

scientific doctrine, we now know that each daughter cell does not receive a complete copy of the parent cell's DNA.

• Each time a cell divides, a portion of the telomere at the end of the chromosome is lost.

• Each new generation of cells have slightly shorter telomeres than their parents. In fact, you can judge the age of a cell by telomere telomere.

• When the telomere gets sufficiently short, the cell dies.

• The telomere serves as a counter or clock for the cell. As the telomere shortens, it changes the behavior of the cell.

• Cells with shorter telomeres begin to slow down. The signals that control hormone output and immune function become weaker and they start to act old.

• When enough cells act old, they create a ripple effect.

• Eventually, the damage progresses to the point that your body can no longer defend itself and succumbs to disease.

Here’s Where the Story Gets Even More Interesting…

• We have discovered an enzyme that rebuilds telomeres.

• With the presence of this enzyme, each dividing cell can build shortened telomeres and any single cell can then divide unlimited.

This Enzyme is Now Known as Telomerase…

• Discovered by Carol Greider and Liz Blackburn in 1985.

• Telomerase is a unique ribonucleoprotein enzyme made of protein and RNA subunits that elongate chromosomes by adding TTAGGG sequences to the end of chromosomes.

• This counteracts the DNA degradation that occurs due to the end replication problem.

Sequence and secondary

structure of the conserved pseudoknot region of human

telomerase RNA.

• This unusual enzyme is a reverse transcriptase that has an RNA template and a catalytic portion.

• It is found in fetal tissue, adult germ cells and tumor cells.

• Telomerase is activated in sperm and eggs until fertilized.

• Fertilization begins a process that will turn telomerase off and then the genetic clock begins to tick.

• Embryonic stem cells express telomerase, which allows them to divide repeatedly and form the individual.

• In adults, telomerase is highly expressed in cells that need to divide regularly, whereas most somatic cells express it only at very low levels in a cell-cycle dependent manner.

• The Hayflick Limit allows for 80-100 total cell divisions per lifespan.

• Almost half of these divisions have occurred by birth.

• This leaves 40-45 remaining divisions between birth and death.

• Telomerase acts as an "immortalizing" enzyme.

• At each round of DNA replication, telomerase adds onto the existing telomeres the nucleotides that would otherwise have been lost, this maintains a constant telomere length.

• Telomerase activity is regulated during development and has a very low, almost undetectable activity in somatic cells.

• When cells do not regularly use telomerase they age.

• If telomerase is activated in a cell, the cell will continue to grow and divide.

Three-dimensional structure of the conserved pseudoknot found in

human telomerase RNA.

Telomerase Activation:• As the embryo matures the telomerase becomes

repressed and essentially “switched off” in all but the germ cells and stem cell populations.

• On the human genome, an enzyme known as human telomerase reverse transcriptase (hTERT) is found on the most distal gene on chromosome 5p.

• The introduction of hTERT into cultured normal human fibroblasts has resulted in telomere elongation, telomerase expression, and the immortalization of these otherwise mortal cells.

• GIVE EVIDENCE NEEDS STUDY

Natural Ways to Activate Telomerase:

There are several strategies that you can put into play today that will help slow the shortening of your telomeres, thus slowing the actual aging process...

Keep your homocysteine level in a healthy range…

• Homocysteine is an amino acid that accumulates in the blood. If you have high levels of this dangerous substance in your bloodstream, you greatly increase your risk of heart disease, Alzheimer's disease, Parkinson's disease, and impotence.

• It's no coincidence that homocysteine levels have been correlated with the most common degenerative diseases of aging.

• Researchers have discovered that high homocysteine tripled the amount of telomere length that was lost during cell division.

• This is tripling the speed at which your body is aging.

• Homocysteine can be measured with a simple blood test.

• Homocysteine levels should fall under 8 but under 7 is even better.

• The following nutrient protocol will correct high homocysteine levels:– Vitamin B12 - 500 mcg

– Folic Acid - 800 mcg

– Vitamin B6 - 25 mg

– Riboflavin (B2) - 25mg

– TMG (trimethylglycine) - 500mg

Vitamin C:

• Our bodies are assaulted by free radicals from the day we are born.

• We have mechanisms that effectively reduce free radicals and correct the damage.

• 2000 mg. of Vitamin C per day can slow the loss of telomeres by preventing free radical damage.

Stress Reduction:• Numerous studies have

linked chronic stress and poor health, including risk factors for cardiovascular disease and poor immune function.

• UCLA scientists have found that the stress hormone cortisol suppresses the immune cells ability to activate their telomerase.

• If the hormone remains elevated in the bloodstream for long periods of time, it wears down the immune system.

• Psychological stress has been shown to cause higher oxidative stress, lower telomerase activity, and shorter telomere length.

• Studies have shown that women with the highest levels of perceived stress have telomeres that are on average, shorter by the equivalent of at least one decade of additional aging compared to low stress women.

To Reduce Stress:• Breathing Techniques can help to calm your body.• Meditation can be a simple and effective way to

focus within yourself. • Make Time for Enjoyable, Relaxing Activities.• Talk About or Write Down Any Concerns that

Cause Anxiety.• Exercise is a great way to relieve stress.• Add other ideas, elaborate or clean up.• Sympathetic vs Parasympathetic balance focus

on breathing

Section on SOD

Newest Breakthrough in Telomerase Activation:

• Over ten years ago, I learned about a biotech company called Geron Corporation.

• They’ve explored the possibility of manipulating telomere length in order to stop cells from aging.

• Ever since they were founded in 1990, they’ve remained at the cutting edge of telomere biology.

• Geron began exploring the possibility of inserting a gene for telomerase into aging cells or developing a drug to turn on the gene for telomerase.

• Info RE: Their genetic manipulation of telomerase

• During their research they hit upon a natural compound that turns on telomerase and rebuilds an aging telomere.

• It comes from an ancient Chinese herb that grows in temperate northern climates.

• It turns out that the herb Astralagus contains small amounts of a molecule named TA-65 that turns on the gene that makes telomerase.

Astragalus tragacantha ssp. Vicentinus

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

• The problem is, you can’t just take Astralagus and stop aging.

• You need a highly concentrated form of TA-65 as an extract.

• It has to be pure, free of toxins, and only comes from certain species of the plant.

P.A.C.E.

P = ProgressivelyA = AcceleratingC = CardiopulmonaryE = Exertion

Exercise with a Different Goal

Interval Training with 3 New Features

• 1. Gradually Shorten Intervals• 2. Gradually Increase Intensity• 3. Train for Gradually Earlier Maximum

Challenge.

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Risk of Death

Exercise Intensity

Exercise Intensity and Risk of Death

Use Anything that Gives Your Heart and Lungs A Challenge

• Running• Rowing• Swimming• Bicycling• Rope Jumping• Calisthenics

• Stair-stepper• Elliptical Machines• Circuit Training• Hindu Squats• Kettle Bells

Are Your Lungs Dying? Adapted from “Biological Aging Measurement,” Dr. Dean Ward. 1988

Age Related Loss of Lung Function

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