TELOMERES, CANCER,

AGING & LIFESTYLE

Dr DEVANAND NATH
MD, M.P.Ed.
CONSULTANT FORTIS
HOSPITAL

TELOMERE
Atelomereis a region of repetitive
nucleotide sequences at each end of a
chromosome, which protects the end of
the chromosome from deterioration or
from fusion with neighboring chromosomes
Forvertebrates,
the
sequence
of
nucleotides in telomeres is TTAGGG. This
sequence
of
TTAGGG
is
repeated
approximately 2,500 times in humans.
Plants also have similar telomeres.

STRUCTURE
Telomeres are the protective caps on the
ends of chromosomes. In young humans,
telomeres
are
about
8,000-10,000
nucleotides long. They shorten with each
cell division, however, and when they
reach a critical length the cell stops
dividing or dies. This internal clock
makes it difficult to keep most cells
growing in a laboratory for more than a
few cell doublings.

TELOMERE

DISCOVERY
Elizabeth Blackburn,
Carol Greider,
and
Jack Szostakwere awarded the 2009Nobel Prize
inPhysiology or Medicinefor the discovery of how
chromosomes are protected by telomeres and the
enzyme telomerase.
Telomeres allow acellto distinguish between
naturalchromosomeends and chromosomebreaks
in order to delay thecell cycleand repair the
broken end. Telomeres also compensate for the
inability
ofDNA
polymeraseto
replicate
thechromosomecompletely.

HAYFLICK LIMIT
Cells stop dividing after a limited
number of divisions. Inhumansthis
occurs on average, after 52 divisions,
known as theHayflick limit. The cell is
then referred to as senescent. Cells stop
dividing
because
thetelomeres,
protective bits of DNA on the end of a
chromosomerequired for replication,
shortenwith each copy, eventually being
consumed.

TELOMERASE
Over time, due to each cell division,
the
telomere
ends
become
shorter.They are replenished by an
enzyme,
telomerase reverse transcriptase.
Shelterin is a group of proteins that
acts as both a positive and negative
regulator of telomere length and as a
negative regulator of telomerase
enzyme activity

TELOMERASE
Embryonic stem cellsexpress
telomerase, which allows them to
divide repeatedly and form the
individual. In adults, telomerase is
highly expressed only in cells that
need to divide regularly especially in
male germ cells but also in activated
lymphocytes
and
certain
adult stem cells,
whereas
other
somaticcells do not express it

TELOMERASE

TELOMERES AND CANCER

Cancercells
have
anenzymecalled
telomerase, present in large quantities
that rebuilds the telomeres, allowing
division to continue indefinitely.
Telomere shortening may also prevent the
development ofcancerin human aged
cells by limiting the number of cell
divisions.
However,
shortening
of
telomeres impairs immune function and
thus might also increase susceptibility to
cancer.

Alternative Lengthening of
Telomeres
However, 510% of human cancers
activate the Alternative Lengthening
of Telomeres (ALT) pathway, which
relies on recombination-mediated
elongation

TELOMERES & BREAST

CANCER
In the Long Island Breast Cancer
Study Project (LIBCSP), authors found
a moderate increase in breast cancer
risk among women with the shortest
telomeres and lower dietary intake of
beta carotene, vitamin C or E.These
results suggest that cancer risk due
to telomere shortening may interact
with other mechanisms of DNA
damage, specifically oxidative stress.

TELOMERES & AGING

Premature
aging
syndromes
includingWerner syndrome,
Ataxia telangiectasia,
Ataxiatelangiectasia
like
disorder,
Bloom syndrome,Fanconi anemia
andNijmegen breakage syndrome
are associated with short telomeres

TELOMERES & LIFESTYLE

A 2013 pilot study fromUCSF showed
benefits of lifestyle changes that
included: a plant-based diet (high in
fruits, vegetables and unrefined grains,
and
low
in
fat
and
refined
carbohydrates);
moderate
exercise
(walking 30 minutes a day, six days a
week); stress reduction (gentle yogabased stretching, breathing, meditation)"
and also "weekly group support".

FACTORS PROTECTING TELOMERES

Dietary intake of antioxidants reduces the rate of
telomere shortening include antioxidants, fiber,
soy protein and healthy fats (derived from
avocados, fish, and nuts) in our diet.
Foods such as tuna, salmon, herring, mackerel,
halibut, anchovies, cat-fish, grouper, flounder,
flax seeds, chia seeds, sesame seeds, kiwi, black
raspberries, lingonberry, green tea, broccoli,
sprouts, red grapes, tomatoes, olive fruit, and
other vitamin C-rich and E-rich foods are a good
source of antioxidants
Impact of fiber, fat, and protein on telomeres
Dietary calorie restriction reduces the pace of
aging

FACTORS PROTECTING
TELOMERES
A controlled body weight: stay
lean, active, healthy through
regular moderate exercise.
Avoid pollutants.
Manage stress.
Meditation.

FACTORS DAMAGING
TELOMERES
In
vitrostudies
have
shown
that
telomeres are highly susceptible to
oxidative stress, and Richter and Zglinicki
presented evidence that oxidative stressmediated DNA damage is an important
determinant of telomere shortening
Smoking, exposure to pollution, a lack of
physical activity, obesity, stress, and an
unhealthy diet increase oxidative burden
and the rate of telomere shortening

TELOMERES AND STRESS

Blackburn also discovered that mothers caring for
very sick children have shorter telomeres when
they report that their emotional stress is at a
maximum and that telomerase was active at the
site of blockages in coronary artery tissue, possibly
accelerating heart attacks.
In 2009, it was shown that the amount of
telomerase
activity
significantly
increased
following psychological stress. Across the sample
of patients telomerase activity in increased
peripheral blood mononuclear cells by 18% one
hour after the end of the stress.

STRESS & DIABETES

A study in 2010 found that there was
"significantly greater" telomerase
activity in participants than controls
after a three-month meditation
retreat.
Telomerase deficiency has been
linked
todiabetesmellitus
and
impairedinsulinsecretion in mice,
due to loss of pancreatic insulinproducing cells.

AVOIDING SEDENTARY
HABITS
A 2014 study entitled "Stand up for
health has found that avoiding sedentary
behaviour might lengthen your telomeres,
irrespective of the time spent on exercise.
Telomere shortening is reversed in
hibernation and aging is slowed (Turbill, et
al. 2012 & 2013). That could be the secret
of Rushi-munis who lived long years in
Himalayas.

MODERATE EXERCISE
Few reports have described the beneficial
effects of physical activity, exercise
training, or acute exercise on telomerase,
shelterin, and other telomere-associated
proteins
In contrast, several lines of evidence in
both immune cells and skeletal muscle
indicate that telomeres may actually
shorten in response to long-term highintensity endurance training.

THE FUTURE
Three routes have been proposed to
reverse telomere shortening: drugs,
gene
therapy,
or
metabolic
suppression,
so-called,
torpor/hibernation.
Targeting
telomerase
immunologically in cancer therapy by
vaccines.

THANK YOU !
devanandnath@gmail.com
7715065555