Adam Cachero, Thien Nguyen, Roby Tanaka
Period 2
11/24/2013
Abstract:
The existence of telomeres was first theorized 51 years ago by Leonard Hayflick. The
telomere is a repeating DNA sequence at the ends of chromatids that is essential for cell division
to occur. Telomerase is an enzyme that adds telomeres back to chromatid. Scientists from T.A.
Sciences developed a new pill to aide in the replenishment of human chromosomal telomeres
called TA 65, similar to the purpose of telomerase. While efficient in replenishing telomeres,
ingesting TA 65 can have many negative outcomes. A future technology that could help
eliminate the risk factor for telomere elongation is utilizing nanotechnology to activate and
deactivate telomerase inhibiting agents. Due to the nanotechnology, overproduction of telomeres
will be manageable.
Present Technology:
A telomere is a repeating DNA sequence located at the ends of chromatids. The purpose
of a telomere is to prevent chromosomes from losing base pair sequences, and to prevent two
chromosomes from fusing to one another. Telomeres are essential to the successful reproduction
and passing on of DNA.1 However, after each cell division, the telomeres on the ends of the
chromatid progressively get shorter. This happens because during the process of DNA
replication, the DNA molecules must unwind into two strands. DNA polymerase is then used to
translate the two strands and make matching strands for both of them. Each new strand is shorter
than before because of the additional space required for RNA molecules. The telomeres of the
1
Shay, J.W. and Wright, W., 1 OCTOBER 11. Roles of telomeres and telomerase in cancer. Retrieved on
November 11, 2013 from, http://www4.utsouthwestern.edu/cellbio/shaywright/publications/Shay%20YSCBI949.pd
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parent DNA molecules were substituted for the RNA, instead of RNA replacing the nucleotides
of the DNA molecule, which could result in a malfunctioning cell, cancer, or cell death.2 After
the telomeres become too short, or reach critical length, the cell dies by a process called
apoptosis.
In 2011, an experiment at the Spanish National Cancer Centre in Madrid, was conducted
on two groups of middle-aged mice. One group was fed food coated with Astragalus
membranaceous, a chinese medicinal plant, and the other group of mice was fed normal food as
the control group3. After a few days, scientists conducting the experiment noticed; after a close
analysis of the mice fed the coated food, that the mice’s telomeres had elongated. This lead the
scientists to believe that this plant possessed telomerase activation potential. After the study,
scientists from T.A. Sciences synthesized a pill called TA 65 that delivers anti-ageing benefits of
telomerase to humans. Based on T.A. Sciences’ research, TA 65 elongates the degrading
telomeres on human chromatids, resulting in increased bone density, stronger immune system,
and decline in any other age-degrading effects4
History:
Telomeres were first theorized to exist by Leonard Hayflick and his observation that
chromosomes were able to replicate right to the tip.5 He contended the Hayflick Limit, an
explanation of the amount of times that human embryonic cells can divide before they succumb
2
Siegal, L.J. 2013. Are Telomeres the Key to Aging and Cancer. Retrieved on November 11, 2013 from,
http://learn.genetics.utah.edu/content/begin/traits/telomeres/
3
Valenzuela, H., 26 SEPTEMBER 2013. New TA-65 Study improves the signs and symptoms of health and
aging. Retrieved on November 12, 2013 from, http://www.revgenetics.com/ta-65/new-ta-65-study-2013
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4
Bhamidi, H., 16 JUNE 2013. Rewinding the Age Clock: Anti-Aging Research. Retrieved on November 17,
2013 from, http://www-scf.usc.edu/~uscience/telomerase_activator_TA65.html
4
5
Watts, W., 18 JUNE 2011. Leonard hayflick and the limits of Ageing. Retrieved on November 11, 2013
from, http://www.news-medical.net/health/Telomere-What-are-Telomeres.aspx
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to senescence. Discovered 51 years ago, it explained the reason for the human age limit and was
evidence that cells had a built in timer that eventually ended in cell death after about 50
replications. However, in lobsters, the telomeres were shown to be renewed by an enzyme called
telomerase. By renewing the telomere caps on chromosomes, it allows the lobster to
continuously age and molt until either predators, or disease kill the lobster.6 This phenomenon
while criticized to negatively affect the human race, can instead focus on other aspects such as a
better understanding of cancers and possibly fix diseases that deal with cell deterioration such as
Alzheimers. With an understanding of the ability for cells to continuously renew telomerase
throughout the afflicted area, humans can manipulate the cancer and stop it’s rampant growth.7
Future Technology:
While the human’s DNA contains the information needed to code for telomerase, the
gene that code for human telomerase reverse transcriptase subunit (hTERT) is repressed.
Without hTERT, telomerase is stuck in an inactive state.8 Thus, telomerase activation required
the overriding of hTERT repression. In order to achieve the objective, nanomachines, robots at
the scale of a nanometer (10-9 meters), are used
While the activation of telomerase is suspected to posses the risk of fueling the growth of
cancer cells as they also exhibit telomerase activities. Nanomachines allow the ability to pick
between normal cells and cancerous cells to activate telomerase unlike the past technique of
consuming telomerase promoting drugs. Through precise programming, these robots are able to
6
Derbyshire, D., 12 SEPTEMBER 13. Do Lobsters Hold the Key to Eternal Life?. Retrieved on November
11, 2013 from: http://web.ebscohost.com/src/detail?sid=e712c01e-80c3-44f2-a2552404eb7e8907%40sessionmgr112&vid=1&hid=117&bdata=JnNpdGU9c3JjLWxpdmU%3d#db=n5h&AN=
90182802
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Stewart, D., 12 SEPTEMBER 13. Could Lobsters help us live Forever?. Retrieved on November 11, 2013
from: http://theweek.com/article/index/249596/could-lobsters-help-us-live-forever
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Wong, J., 12 SEPTEMBER 13. Telomere maintenance and disease. Retrieved on November 11, 2013
from: http://web.ebscohost.com/ehost/detail?vid=8&sid=836566f2-3e0d-4627-81f51eff90e9290c%40sessionmgr11&hid=28&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=voh&AN=10
873211
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enter human somatic cells and into the nucleus. When inside the nucleus, nanomachines will
promptly inhibit hTERT repressor’s activities and allow the transcription of hTERT. With
nanomachines as the inhibitor, the process can be easily reversed by stopping their activities and
allowing the hTERT repressor to function again.
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Breakthroughs:
While the important subunit hTERT for telomerase has been determined to be repressed
inside the human’s DNA, hTERT repressor has yet to be discovered8. Therefore, in order to fully
activate telomerase, hTERT repressor needs to be determined through 2 hints. The first hint that
might open the door to the repressor is the fact that telomerase activities disappear from human
somatic cells beyond early fetal development.9By pinpointing the time of the disappearance and
what’s happening during that time, it might be possible to determine the repressor. The second
hint toward the discovery is the chemical component of the drug TA 65 which has the ability to
elongate degrading telomere.4 While it’s confirmed to induce telomerase effects, there’s no study
on the exact process on how the drug does so. Thus, by exploring into the the exact interaction it
have with the human body, it’s possible to determine hTERT repressor as it’s most likely that the
drug affects the repressor to produce such effects.
Another important factor to the activation of telomerase is the technology that it’s going
to use. Nanotechnology is a relatively young concept that only gained publicity since 198610.
With such a short history, the technology is still largely in research and development phase with
the greatest challenge on how to actually create it. With the scale of 10-9 meters, it’s likely to be
impossible to be built using modern days equipments11. However, with the studies of top down
and bottom up approaches, scientists have been slowly moving forward the ability to create such
machine11. By opening the door to nanomachine creation and manipulation, it’s possible to
activate telomerase.
Design Process:
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With the amount of room opened for imagination, it’s impossible for each member to
have the same idea about the technology. Therefore, the first and foremost action was to get
everyone’s vision on the project. Through side by side analysis, it was easy to determine the
strengths and weaknesses of each idea and use them to design the most appropriate plan. While
they were discarded, rejected ideas are still stepping stones that worth mentioning.
The first alternative was to extract telomerase from other species and inject it into human.
However, it was rejected due to uncertainty on how telomerase will move and spread through the
body. Furthermore, it possesses the risk of telomerase interacting with cancerous cells and
escalate their activities.
Another alternative idea was to explore the mechanism that allows cancerous cells to
exhibit telomerase activities. While it seemed plausible at first, the idea was scrapped due to the
fact that cancerous cells contain mutations. Thus, normal somatic cells might not behave the
same way if they undergo treatment derived from cancerous cells. Additionally, the treatment
itself might be able to convert normal cells into cancerous ones.
An idea that was accepted at first was to alter human’s DNA to code for the
synthesization of telomerase. It was an interesting and popular idea that driven the project during
its planning phase. However, with further research, it was discovered that it’s already in the
human’s DNA and the idea was rejected. But, it raised the question on the reason why it’s not
expressed even though it’s in the DNA and what can be done to express it.
Consequences:
Telomerase could very well be the cure to many problems that afflict the human race.
Diseases like Alzheimers could be cured and cancer could be a thing of the past. By targeting
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the cells that are affected by the deterioration of the cells, we can slow and possibly even stop
these diseases from progressing and maybe even eliminate it from society as a whole.
Alzheimer's, a type of dementia, is a disease that affects the brain and is caused by brain
cell death.9 The subject with Alzheimer’s will experience a deterioration of memory due to the
cell death and the shrinking of the brain over time. The minimized brain mass results in fewer
nerve cells and connections to trigger memory. However, with the incorporation of the enzyme
telomerase, we can prevent the deterioration of the brain and actually grow brain cells and cause
neurogenesis10 instead of allowing the brain to deteriorate. However, with the use of telomerase,
there could also be other problems with the duplication of brain cells. Tumors are a major
concern with the use of telomerase with the fact that telomerase could possibly mutate into the
genetic material of the cancerous cells of the tumors and go completely against what is trying to
be accomplished. However, in order to prevent this, the nanobots we are using to implement the
telomerase will only target cells in dire need of it. If the robot detects any cells that do start
mutating with the telomerase, it will eradicate the cell that is being mutated. The effect on
society by clearing Alzheimer’s is that there will be a greater part of the population that will be
able to function in society after the age of 85 years of age. This will increase the quality of life
of the people around the individual and they will be allowed to function the same as anyone else
in that age group.
Cancer would be better understood with the knowledge of how telomerase works.
Certain forms of cancer have been found to be able to create their own version of telomerase and
multiply indefinitely. The tumor cells that are found to create telomerase can be studied to figure
MacGill, M., 1 NOVEMBER 13. What is Alzheimer’s disease? Causes, symptoms and treatment. Retrieved
on November 24, 2013 from: http://www.medicalnewstoday.com/articles/159442.php
10
Cherry, K., 25 SEPTEMBER 13. Can People Grow New Brain Cells?. Retrieved on November 24, 2012
from: http://psychology.about.com/b/2013/09/25/can-people-grow-new-brain-cells.htm
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out how to better combat them.11 hTERT can be used to deactivate the telomerase in tumor cells
and better manipulate the cells for our use. The downside to using this is that the average
lifespan will go up and thus population will increase. This negatively affects society because the
speed at which resources will increase and the effect on the world will be drastic. As a result, the
natural balance that humans have between living on this planet and depleting its resources will
be changed.
11
Shay, J., 22 JANUARY 01. Telomerase and Cancer. Retrieved on November 24, 2013
from:http://hmg.oxfordjournals.org/content/10/7/677.full
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