FREE ESSAY ON TELOMERE AND TELOMERASE

TELOMERE AND TELOMERASE

An Introduction To Telomere and Telomerase 
The telomere-telomerase hypothesis of aging and cancer is based on the findings that most
human tumors have telomerase activity while normal human somatic cells do not.
An emerging hypothesis is that the up regulation or reexpression of telomerase is a
critical event responsible for continuous tumor cell growth. In contrast to normal cells,
tumor cells show no loss of average telomere length with cell division. Through this
suggestion immortalization may occur through a mutation of gene in the telomerase
repression pathway allowing the expression of telomerase in cancer cells.
Telomerase is a ribonucleoprotein enzyme which stabilizes telomer length by adding
hexametric(TTAGGG) repeats to telomeric ends of the chromosomes, thus compensating for
the continued erosion of telomeres that occurs in its absence. Telomerase is normally
only in cells that give rise to sperm and egg or in some stem cell lines, it maintains
the integrity of the chromosomes. the sex cells are the only part of the body that are
biologically required to be immortal, because if there was a progressive loss of
chromosomes with each generation then this would lead to extinction. However when cells
become cancerous, the enzyme telomerase is activated, this enables the cancerous cells to
replicate without a limit and this process makes the cells immortal.
According to a research done by a team of researchers at the University of Texas, 
An evaluation of cell lines from 18 different human tissues revealed the presence of
telomerase in 98 of the 100 immortal cell lines, telomerase was not found in any of the
22 mortal cell lines. 
Telomeres is a repeated DNA sequence(TTAGGG) found at the ends of linear chromosomes that
protect the ends of the chromosome from degradation, or telomere can be defined as DNA
sequences found at the ends of eukaryotic chromosomes which maintain the fidelity of
genetic information during replication. At birth as determined by terminal restriction
fragment analysis, telomeres consist of about 15,000 base pairs of repeated TTAGGG DNA
sequences, which become shorter with each cell division owing to the end replication
problem. Every time a cell divides it loses 25-200 DNA base pairs off the telomere ends.
once this pruning has occurred about 100 times a cell ages and does not continue to
divide. It has been proposed that telomere shortening may be a molecular clock that count
the number of times a cell has divided and determines when cellular senescence occurs
(cellular senescence is the limited capacity of cells to divide beyond a finite number of
population doubling. In a lay man's understanding this means cellular death. Normal
diploid human cells have limited capacity to proliferate (are mortal).
There appear to be two mechanisms responsible for the proliferative failure of normal
cells. The first, mortality stage 1, occurs when there are still at least several
thousand base pairs of telomeric sequence left at the end of most of the chromosomes. It
is possible that mortality stage 1 may be induced by the activation of genes located in
the immediately 
subtelomeric region of the chromosomes. 
The second is the mortality stage 2 which represent the physiological result of
critically short telomeres when cells are no longer able to protect the ends of the
chromosomes, so that the end degradation and end to end fusion occurs and causes genomic
instability and cell death). 
While researching on a topic like this, couple of important questions came to mind, so I
made effort to research and address some of these questions which might be considered
important.
One of such questions is why do telomeres shorten? 
the mechanism of DNA replication is different in linear chromosomes is different for each
of the two strands, known as leading and lagging strands. the lagging strand is made as
series of discrete fragment, each one requiring a new RNA primer to initiate synthesis.
the DNA between the last RNA priming event and end of the chromosome cannot be filled in.
{this process is known as the end replication problem} since a strand cannot copy its
end, telomeres shortening is required to occur during progressive cell divisions. the
shortened telomeres are inherited by daughter cells and process repeats itself again.
The mind may inquire if stopping the shortening of telomeres whether that will prevent
the body parts from aging; according to researchers, slowing down the rate of telomere
shortening might help reduce the extent at which the body ages. An experiment done by a
group of researchers from the University of Texas helps clarify this statement in full,
hybrids between immortal cells that express telomerase, and normal cells that lack
telomerase, creates a cell with limited lifespan. Also experiments show that treatment of
immortal human cell lines with oligonucleotide will resulted in telomere elongation.
Using this finding, the researchers tested the hypothesis that elongation of telomeres
could extend the lifespan of a cell, this was done by treating an immortal human cell
line with oligonucleotides to lengthen its telomere, and then fusing the cell to a mortal
cell. this experiment showed that the hybrid cells had a longer lifespan, than the
hybrids without elongated telomeres. This gives the hypothesis that telomere length may
determine the human lifespan.
Many might not know, but telomerase pays an important part the longevity of cancer cells,
which makes it one of the prominent aids in the ability of cancer cells to thrive. The
enzyme telomerase aids cancer cells by halting the telomere shortening in cancer cell,
thereby allowing the cell to divide indefinitely. Scientist are struggling to develop a
therapy to inhibit telomerase activity in cancer cells which they believe will force the
cells into a normal pattern of senescence and death. 
Someone might ask if it where possible to revert old cells into young cell: according to
my research, technically its possible, thus if cells are completely senescent it may not
be possible to get them to grow again even if the telomere is elongated, however
telomere's are rate limiting for growth, so a few division may do the trick of resetting
the clock.
Due to the fact that telomerase aids cancer cell, an individual might ask why the
introduction of telomerase not lead to cancer?
First a fact should be stated that telomerase are found present in specialized
reproductive cells and most cancer cells that appear to divide indefinitely, but the main
function of telomerase is to maintain telomeres and permit continued cell growth. 
So its important to understand that cancer is caused by accumulation of several
alterations that occur over a lifetime, and which affects processes controlling cellular
growth rates, and ability to invade and undergo metastasis, while telomerase only affect
the counting of the number of times a cell has divided, not the rate of cell growth. thus
all telomerase do is permit continued cell growth that would otherwise be limited by
shortened telomeres, so that does not make it a cause of cancer.
Another question that personally i was interested in while researching about telomerase
is " would telomerase therapy attack other cells such as reproductive cells?
According to my research anti telomerase therapy could affect germ line {reproductive
cell and possibly stem cells of renewal tissues {basal cells of skin}. but luckily the
telomeres of such cells have longer telomeres than cancer cells, so it might be possible
to inhibit telomerase in cancer cells and cause their death, without causing the other
cells to run out of telomeres.
Another situation, i feel will be of great inquiry among knowledge filled minds is;
according to multiple researches, its been proven that not all cancer sells express
telomerase, if so how are they maintaining their telomeres growth?
Scientists state that approximately 85-90% of cancer cells displays telomerase activity,
which brings us back to the main question. According to scientific researchers cancer
cells, which do not show sign of telomerase activity, may be involved in one of these
activities:
1, the cell may not have yet been immortalized, thereby making the appearance of
telomerase activity absent.
2, also lot of scientist believes that some cancer cells have an alternative pathway for
maintaining telomeres. This telomere is believed to be of heterogeneous length, varying
from big to small, and this aiding as confusion to the structure responsible for cell
death.
One of the main focus of researchers in the study of cancer is using the detection of
telomerase activity to predict cancer; telomerase activity is easily detected in many
pre-malignant specimens (lung and breast cancer), while colon and pancreatic cancers
can't be detected until later stage. The ability to use almost any clinical specimen and
to demonstrate telomerase may allow the detection of cancers at an earlier stage.
much progress has been made in the development of more accurate molecular based cancer
tests to assess tissue specimen. unluckily most of this method do not have sufficient
specificity (ability to differentiate between normal, precancerous, and cancerous cells)
and sensitivity (accuracy in detecting the presence of cancer) to identify a wide variety
of cancer types. Therefore, new clinical method, applicable to all cancer types is
needed.
currently researchers are working on that, though a product called a PCR based telomerase
method was produced in 1994, it still had a couple of little set backs and didn't live up
to its expectation fully.
Finally a question, which must be of interest to anyone interested in the evolution of
telomerase, is how long before telomerase can have a medical impact, such as cancer
screening/ telomerase therapy?
This is a statement i found in the internet addressing the question, "since telomerase is
detected in almost all tumors and in some cases early in the development of the cancer,
then early cancer detection using telomerase may be a promising approach. 
There are already a number of situations where knowledge of the presence of telomerase
may have value in risk stratifying patients into those that are likely to have favorable
outcomes and those that are not. There is a major effort at the national cancer institute
to establish a series of molecular markers for cancer, and it is expected that within a
few years we will have perhaps one hundred or more molecular markers that may indicate
the presence of cancer. Its predictable that within the next ten years, scientist will be
able to take a few cells, do micro array analysis and determine not only if a person has
cancer, but also the type of cancer, the genes that are altered, and hopefully a
therapeutic 
method that goes to work and destroy the cancer immediately".
Conclusion:
While there is justifiable optimism regarding telomerase activity, its important to
understand that their is still much to acquire about this enzyme, and additional
validation studies will be required before knowledge of telomerase can be used to the
fullest in medical practice. Finally the utility of inhibitors of telomerase in the
therapy of cancer is awaited to with great anticipation.
Note- even though telomerase aids cancer cells in longetivity (avoiding cell senescence)
still telomerase as an enzyme has nothing to do with the development of cancer cells, its
just a helping aide, so all blames should not be put on it.
REFERENCES:
Shay JW: Telomerase activity in human cancer. 1996
Bacchetti S, counter CM: telomerase: a key to cell immortality. 1995
And a whole lot of notes taken from Internet site.