Telomeres are repetitive nucleotide sequences located at the ends of chromosomes that protect them from deterioration. They consist of the sequence TTAGGG repeated hundreds to thousands of times. Each time a cell divides, the telomeres shorten due to an inability to fully replicate chromosome ends. This represents a biological clock for cell division. Telomerase is an enzyme that adds telomere sequences and prevents shortening, allowing cells to avoid replicative senescence or death. In cancer cells, telomerase is often reactivated, allowing unlimited cell division by maintaining telomere length. Telomeres play a key role in cellular aging and are also implicated in many diseases.

2. TELOMERE
POOJA S NATHAN
S4 BT 25

3. The functional units: Genes
▪ Genetic information, or
"genes,” are a series of
bases called adenine
(A), guanine (G),
cytosine (C), and
thymine (T).
▪ These base pairs make
up the sequences, or
instructions needed to
form proteins, our
cellular machinery.

4. What is a human telomere?

5. ▪ Telomeres are repetitive nucleotide sequences located at the
terminal of linear chromosomes of most eukaryotic organisms.
▪ Its name is derived from the Greek nouns telos ='end' and merοs =
'part’.
▪ Most prokaryotes do not have telomeres.
▪ When they are completely worn away, the cell is destroyed.
▪ Telomerase provides the necessary enzymatic activity to restore
and maintain the telomere length.
▪ Telomeres consist of variable numbers of a repetitive sequence,
(TTAGGG)n. This sequence of TTAGGG is repeated
approximately 2,500 times in humans.
▪ Telomeres are stabilised by the aptly named protein complex,
shelterin (de Lange, 2005).
▪ In humans there are 46 chromosomes and thus 92 telomeres (one
at each end) in a single cell.

6. Discovery

7. Function of Telomere
▪ They protect the chromosomes.
▪ They separate one chromosome from another in the
DNA sequence
▪ Without telomeres, the ends of the chromosomes
would be "repaired", leading to chromosome fusion
and massive genomic instability.
▪ Telomeres are also thought to be the "clock" that
regulates how many times an individual cell can
divide. Telomeric sequences shorten each time the
DNA replicates.

8. Think of it like this….
▪ Telomeres effectively "cap" the end
of a chromosome in a manner
similar to the way the plastic on the
ends of our shoelaces "caps" and
protects the shoelaces from
unraveling. (Geron corporation)

9. Telomeres & Aging
Healthy human
cells are mortal
because they can
divide only a finite
number of times,
growing older each
time they divide.
Thus cells in an
elderly person are
much older than
cells in an infant.

12. 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. 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-replicationproblem.

13. End-replication problem

15. Dna replication

16. • DNA replication does not begin at either
end of the DNA strand, but starts in the
center DNA polymerases move in the 5'
to 3' direction, there is a leading and a
lagging strand on the DNA molecule
being replicated.
• On the leading strand, DNA polymerase
can make a complementary DNA strand
without any difficulty because it goes
from 5' to 3'.

17. • However, there is a problem going in the other
direction on the lagging strand. To counter this,
short sequences of RNA acting as primers attach to
the lagging strand a short distance ahead of where
the initiation site was.
• The DNA polymerase can start replication at that
point and go to the end of the initiation site. This
causes the formation of Okazaki fragments.
• More RNA primers attach further on the DNA
strand and DNA polymerase comes along and
continues to make a new DNA strand.

18. • Eventually, the last RNA primer attaches, and
DNA polymerase, RNA nuclease, and DNA
ligase come along to convert the RNA (of the
primers) to DNA and to seal the gaps in between
the Okazaki fragments.
• But, in order to change RNA to DNA, there must
be another DNA strand in front of the RNA
primer. This happens at all the sites of the lagging
strand, but it does not happen at the end where
the last RNA primer is attached.

19. • Ultimately, that RNA is destroyed by
enzymes that degrade any RNA left on the
DNA. Thus, a section of the telomere is lost
during each cycle of replication at the 5'
end of the lagging strand's daughter.
• Thus, a section of the telomere is lost during
each cycle of replication at the 5' end of the
lagging strand's daughter.

21. SOLUTION TO
END REPLICATION PROBLEM

22. TELOMERASE
▪ Telomerase enzyme adds bases to the
ends of telomeres.
▪ Specialized reverse transcriptase.
▪ In young cells, telomerase keeps
telomeres from wearing down too much.
But as cells divide repeatedly, there is not
enough telomerase, so the telomeres grow
shorter and the cells age.

23. • Telomerase is turned off in somatic cells
• But remains active in sperm and eggs,
which are passed from one generation to
the next.
• If reproductive cells did not have
telomerase to maintain the length of their
telomeres, any organism with such cells
soon would go extinct.
• Telomerase activity is low or absent in
normal cells, when compared to cancer cell.

24. 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 acquire 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.

25. • The 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 lengthening &
proliferative growth.
• Telomerase is over expressed in many
cancers cells.

27. factors that may influence telomere length

28. Diseases Affected By telomere Shortening
Cardiovascular
Cancer
COPD
Degenerative Disc Disease
Alzheimer’s
Osteoarthritis
Rheumatoid Arthritis
Osteoporosis
General Immunity
Skin Aging
Macular Degeneration
Liver Cirrhosis
Muscular Dystrophy
Cell & Tissue Transplants
AIDS
Progeria
Dyskeratosis Congenita
Idiopathic Pulmonary Fibrosis
Cri du Chat syndrome
Down’s Syndrome
Fanconi’s Anemia
Tuberous Sclerosis
Werner’s Syndrome
And, Aging Itself???????

29. •Right Exercise
•Anti-Oxidants
•Omega 3’s
•Vitamin D3
•Don’t Smoke
• Weight
Management
• Reduce Stress
• Reduce Depression
• Reduce Pessimism
• Be Happy!
Keeping Telomeres Long

30. Unlocking the telomere is the MOSTimportantevent in the historyof anti-aging
medicine

31. THANK YOU