Telomeres cap the ends of chromosomes and protect them from degradation during cell division. As cells divide, telomeres shorten due to the inability of DNA replication enzymes to fully copy chromosome ends. This limits a cell to around 50-70 divisions before entering senescence. Cancer cells activate telomerase to maintain telomere length, allowing unlimited division. Telomeres play a key role in both aging and cancer - their shortening limits the lifespan of normal cells but cancer cells overcome this via telomerase to achieve immortality and uncontrolled growth. Measuring and targeting telomerase may provide new strategies for cancer detection and treatment.

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Introduction:
The major function of telomere is to cap the ends of chromosomes and protect the chromosomes
from RED mechanism. As cells divide, telomeres continuously shorten with each successive cell
division. Telomerase provides the necessary enzymatic activity to restore and maintain the
telomere length. The vast majority of tumour's activate telomerase , and only few maintain
telomeres by ALT mechanism relying on recombination. Telomere and telomerase are the
attractive targets for anti-cancer therapeutics.
Why senescence occurs in eukaryotic organisms?
Our bodies are composed of more than a billion cells. Cells are continually dying and new cells
are continually being formed Inside the nucleus of a cell, our genes are located on twisted,
double-stranded molecules of DNA called chromosomes. Unique structures at the end of
chromosomes are necessary for chromosomal integrity and overall genomic stability called as
telomeres which protect our genetic data, make it possible for cells to divide, and hold some
secrets to how we grow old and get cancer. An entire chromosome has about 150 million base
pairs. Each time a cell divides, an average person loses 30 to 200 base pairs from the ends of that
cell's telomeres

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This is because enzymes that duplicate DNA cannot continue their duplication all the way to the
end of chromosomes. If cells divided without telomeres, they would lose their ends of
chromosomes and necessary information they contain.Cells normally can divide only about 50 to
70 times, with telomeres getting progressively shorter until the cells become senescent, die or
sustain genetic damage that can cause cancer.
Example: In human blood cells, the length of telomeres ranges from 8,000 base pairs at birth to
3,000 base pairs as people age and as low as 1,500 in elderly people. Telomeres do not shorten
with age in tissues such as heart muscle in which cells do not continually divide.
 Telomere structure:

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Telomeres are comprised of repeat sequences and bound by multiple telomeric interacting
proteins. In mammalian cells, telomere DNA contains double-stranded tandem repeats of
TTAGGG followed by terminal3¹ G-rich single-stranded over- hangs. Telomere DNA is thought
to adopt the T-loop structure, where the telomere end folds back on itself and the3¹ G strand
overhang invades into the double-stranded DNA(these-called D- loop).
Why do telomeres get shorter each time a cell divides?
 Before a cell can divide, the chromosomes within it are duplicated so that each of the two
new cells contains identical genetic material. A chromosome's two strands of DNA must
unwind and separate.
 While replicating DNA, the eukaryotic DNA replicating enzymes, cannot replicate the
sequences present at the end of chromosomes. Hence these sequences and the information
they carry may get lost.
 They cap the end sequences and themselves get lost in the process of DNA replication.
 In 1972, James Watson called this as End-replication problem.
 The first step is to unwind their double helices into separate strands. As the double helix of
DNA unwinds into two parent strands, the ends of the different bases are exposed. Due to the
obligatory pairing of A-T and G-C, each parent strand becomes a template for copying a
whole new DNA helix.
 Since the DNA structure can be rebuilt on both parent strands, two identical DNA helices
are produced, each containing one original parent strand and one newly synthesized strand,
called a complementary strand.
 Due to the nature of the mechanism via which DNA is replicated, one strand of the DNA is
left with an incompletely replicated end. Without specialized means of

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maintaining chromosomes, this causes chromosome ends to shrink with each successive cell
division.
What role do telomeres play in cancer?
 Telomeres were first discovered in cancer cells because, cancer cells are saturated with an
enzyme called telomerase.
 Telomerase is the key enzyme for human cells to accquire immortality.
 As a cell begins to cancerous, it divides more often and its telomere becomes very short. If its
telomeres get too short, the cell may die, whereas normal cell is devoid of telomerase
activity.
 It can escape this fate by becoming cancerous cell by activating telomerase (or) ALT
pathway is activated, resulting in abnormal telomere lengthen & proliferative growth
 Telomerase is over expressed in many cancers cells.
 When cells lose the function of P53 pathway, they can no longer arrest cells in G1 an
important point in cell cycle for repairing DNA damage response. Cells without P53 are able
to divide with deprotected telomeres, which cause genomic instability a common feature of
malignant cells.
Role of telomeres in aging?
Aging is a degenerative process that is associated with progressive accumulation of deleterious
changes with time, reduction of physiological function and increase in the chance of disease and
death.
 Some long lived species like human have telomeres that are much shorter than species like
mice, which live only few years.

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 But its evidence shows that telomeres alone, do not reduce the life span, but there are some
factors which also plays an important role in aging.
 Cawthon´s study, found that, when people are divided into 2 groups based on telomere
length, the half with longer telomere lives five years longer than the shorter telomeres. That
suggests lifespan could be increased five years by increasing the length of telomeres in
shorter one.
 Short telomeres are linked to higher risk of age related diseases.
 Stressful life experiences in childhood and adulthood have been linked to accelerate telomere
shortening.
 Long term unemployment may accelerate aging in men.
 The major cause of aging is ʻʻOxidative stressʼʼ and ʻʻGlycationʼʼ.
 Mitochondrial dysfunction also plays an important role in aging and age related diseases.
 Protein misfolding can also cause age related disease as we grow old
The below graphs shows human life span has increased from1700ˊS with an average of
5years

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Conclusion:
 Measuring telomerase may be a new way to detect cancer.
 If scientists can learn how to stop telomerase, they might be able to fight with cancer by
making cancer cells age and die.
 Some of the drugs are showed positive results by inhibiting telomerase and associated
proteins and finding the way to shortening of telomere which results in cell death/apoptosis.
 Most of anti-telomerase drugs are still in Clinical phases I and II.