By Dave Woynarowski, MD, CPT
Ever since the dawn of man the desire for eternal life has been a compelling dream. From Methuselah to Ponce de Leon to Dorian Gray, stories of what might happen if man could live for extended periods have permeated every culture and every consciousness.
But it has only been in the last 50 years that the sobering reality of death has bumped up against a real hope for a longer disease and pain free life. It all began ironically enough with a question. A young scientist at the Wister Institute in Philadelphia named Leonard Hayflick wanted to know whether human cells were really immortal as was then the accepted dogma.
Hayflick found that normal human cells can only divide a certain number of times and accordingly have a finite life span that under ideal conditions could allow a person to live for approximately 120 years.
The number of times a cell can divide became known as the Hayflick limit.
It took more than 20 years before the actual mechanism of the Hayflick limit began to be understood and another 20 before it was completely explained.
While over simplified, the nature of cellular aging and thus the aging of the human organism can be summed up by the "biological time clock theory."
There is a natural biological time clock in every single cell in the body. This "time clock" resides in a simple end cap sequence of repetitive DNA known as the telomere.
The telomere functions to keep our DNA in its optimum double helix form. It also acts as a primer sequence that allows proper replication of the DNA when the cell divides.
Unfortunately with each and every replication of our DNA, part of the telomere sequence is chopped off. It is in this "chopping off" that the key to aging has been found.
For a better perspective let's look at conception, birth and finally death from a cellular standpoint.
When we are conceived the union of sperm and egg has some 15,000 base
pairs in its telomeres. After many replications a newborn human is
formed and born with approximately 10,000 base pairs in each telomere
sequence.
Thus in the uterine development of a human, when
cells are dividing
furiously to make a newborn baby, 5000 base pairs of telomere length
are lost. In a sense we start to die the minute we are conceived!
During the continuum of human life the trillions of cells that make up
a person continue to divide, grow and replicate. With each cell
division a few base pairs of DNA are lost until when the critical limit
of approximately 5000 base pairs is reached, the cell is no longer able
to divide. Then one of two things happens; either it enters a phase
called senescence, which is like retirement, where the cell doesn't work
anymore but is still alive or the cell commits suicide (apoptosis) and
dies.
Whether senescent or dead, such cells are obviously no longer able to
function. If one extrapolates this process to billions of cells within
each organ system, we can see why organ function declines with age and
eventually people wear out.
Even if we never contracted a disease of any kind, we would eventually
wear out because of this mechanism. The oldest man has lived to 113
years and the oldest woman, Jeanne Calment, actually exceeded the
theoretical Hayflick limit by reaching an age of 122 years before
passing away in 1997.
But such people were clearly anomalies as most of us will die before
reaching the age of 85.
Why?
The answer to this question may lie in a combination
of Telomere
Biology and the insight of Shakespeare! In Hamlet when the bard wrote
the phrase, "The slings and arrows of outrageous fortune," he may have
unknowingly been describing the mechanism that will eventually kill
most of us.
Stress, environmental exposure to toxins including UV radiation,
excesses of drink, tobacco, drugs, and food, lack of sleep, and of
course physical trauma all accelerate the cellular replication process.
The body trys to maintain a normal compliment of functioning cells
and our behavior or sometimes simply the slings and arrows of our
environment and our misfortunes forces our cells to replicate faster
and in larger quantities than would be "normal." That accelerates the
march toward reaching our finite Hayflick limit which under perfect
conditions equals about 120 years.
Each cell replication accelerates telomere shortening and each
replication brings us one step closer to death.
Our current average lifespan of around 80 years (in America) is caused
by the interplay between telomere length, "average" genetics, and
environmental factors.
While the direct correlation of telomere length and disease process in
humans is generally not understood, there is now overwhelming evidence
that people with diseases associated with aging have shorter telomeres
than healthy people. And the other theories of aging can't account for
this fact.
The free radical theory of aging postulates that cumulative free
radical damage to cells causes aging and eventually death. Clearly if
an organism had unlimited ability to replicate and replace damaged
cells with healthy ones, free radicals would cease to be an issue.
Also intriguing is the fact that human cancer cells, even though
immortal, have very short telomeres, which allows the DNA orientation
to change and gene expression to change thereby unmasking oncogenes and
encouraging mutations.
More research is needed in the area of telomeres and disease but the
emerging evidence points to the benefits of maintaining a telomere
length that is above the critical level of 5000 base pairs at which
point cells go into a state of "crisis."
All of this begs the question: what would happen if we could stop
telomeres from shortening or maybe even lengthen them in spite of
advancing chronological age?
There is in fact a mechanism where this can be done. Humans and all
other mammals have an enzyme known as telomerase that can lengthen the
telomere ends and thus slow down the loss of telomere base pairs.
The activity of telomerase sensibly varies with the divisional activity
of the different cell types. For instance immune system cells have
highly active telomerase and can rapidly divide when the body senses
foreign bacterial
or viral invaders. Stem cells also have a high level
of telomerase capacity. But most other normal somatic cells have very
low levels of telomerase.
But in any case, the normal activity of telomerase is not sufficient to
mitigate against the inevitable loss of telomere base pairs and the
resulting senescence or apoptosis (programmed death) of our cells.
The search of a safe compound that activates telomerase in humans has
been going on for about 10 years, paralleling other scientific research
in the new field of telomere biology.
There is of course much controversy surrounding the moral, social, and
biologic ramifications of lengthening human telomeres and everything to
do with the science of Telomere Biology is still viewed by many as
being "experimental."
Fortunately that "experiment" is actually taking place at a company in
New York known as T.A. Sciences which markets the first, and currently
the only, proven telomerase activator safe for human consumption. This
telomerase activator (TA-65) is only sold through select doctors
licensed by the company and it is expensive.
TA-65 is derived from the astragalus root, which has been used in
Traditional Chinese Medicine for many, many years. It is a purified
single molecule isolated from the thousands of other molecules present
in the plant. It appears to be very safe for human consumption
(no adverse effects have been reported to date) and the company has
data that show lengthening of the specific telomeres that cause all the
problems. Those are the shortest telomeres; it only takes a single
short telomere to send a cell into crisis.
Scientists at other companies and in university labs all over the world
are now looking for other compounds- both synthetic and natural- that
will lengthen the telomere, but nothing else has yet been discovered
that can be used in a safe, commercially available preparation.
As more and more research is done in the area of Telomere Biology, the
mechanisms of human aging will become clearer and the applications for
disease treatment as well as life extension will become more apparent.
Untangling the mysteries of Telomere Biology will not stop people from
drinking, smoking, stressing, or simply overdoing it (extreme forms of
exercise like running Marathons actually shortens telomere length). All
such activities amount to burning the candle at both ends and putting
overindulgent people into early graves. But for those of us who lead
healthy lives, the ravages of old age are still waiting for us.
Telomeres and telomerase are at the crux of human aging and telomerase
activating products like TA-65 offer the only current opportunity to
delay our own meeting with the Grim Reaper.
Dave Woynarowski, M.D., CPT, is the Chief Medical Education Office for T.A. Sciences and is an ultra runner who takes TA-65 to boost his
athletic performance. On Aug. 2, Dr. Dave ran 30 miles across the
Canadian Rockies as part of the Death Race 2009 to raise money for his
charity, www.TheRaceAgainstDeath.org benefiting handicapped athletic
kids and to prepare for his 50th birthday in September!