Genomic Connections with Aging

Sri Hari Prasad Sirigina

SID 101-99-323

Introduction:
Every One might wonder what is the reason for aging and how the wrinkles show up, hair
becoming white, and why does the man become weaker as the days passed by. There are several
external reasons like exposing the body to the pollution, lack of physical exercises to the body.
Many scientists believe different reasons for the aging like damage to the DNA, accumulation of
dna, loss of the elasticity in the tissues, mitochondrial damage, due to the presence of highly
reactive oxygen molecules.

Aging is completely a new phenomenon. Man has his evolution for many centuries. At the
ancient years of man evolution his life expectancy is very less like around forty years because of
their lack of development in the medical field. At the early stages of life, the life expectancy is
very less and started increasing till today because of the advancement in the medical field.
Observations on the human growth from all these years have revealed that the life expectancy
has increased in equal intervals of five years for each evolution .The life period started increasing
unless there are any natural frontiers like plague that effected the years of evolution.

We can observe in the above graph between age and survival. The life expectancy or the survival
rate is very maximum during the time of birth and it goes on decreasing exponentially during the
aging but the decrease is less exponential for the next generations because of the care and control
of the health.

Free Radical Theory of Aging:

There are many theories proposed by the Scientists based on their observations like Free Radical
Theory of aging, Telomere theory of aging, Cross Linking Theory of aging, Anti aging theory,
acidification theory of aging. Scientists have observed the relation between the ages of human
aging and the life expectancy which states that the possibility of the life expectancy during the
birth is maximum and it exponentially decreases because of Aging and by observing the different
exponential curves during the evolution revealed the facts that during all these years the life
expectancy is maximum at the birth and it decreased but slowly because of the sophisticated life
and the advancement in the Technology.

Denham proposed Free Radical Theory of aging in 1956. Free radicals cause damage to the cells
by damaging and destructing the cells. These free radical cells kill the cells and cause aging. This
process is called as thieving of oxygen. At normal process when the oxygen enters the body it
enters into all the parts of the cell and finally the oxygen enters into the mitochondria, which are
also called as the powerhouse of the cell. The mitochondrion takes the oxygen and generates the
energy responsible for functioning of the cell. Oxygen always needs the four electrons to form
the water molecule .If the oxygen molecule without the presence of electrons becomes very
reactive and unstable. This highly reactive and unstable molecule is called as free radical.

Absence of electrons causes a free radical, which is responsible for the primary damage of the
cell and finally causes the death of the cell. The free radical tries to attack the cells and tissues of
the body and make them unstable by capturing the electrons of unstable molecules. In order to
get rid of this highly reactive molecule we need to produce anti oxidants, which can supply free
electrons to these radicals and thus can stabilize the free radicals.

Anti Oxidants:
Anti Oxidants are the substances, which react with the highly reactive free radicals that are
produced every day inside the body. These Anti Oxidants react directly with oxidants inside the
cell and protect the cells, tissues from being damaged. These Anti oxidants supply the free
electrons to the unstable oxidants and make them stable. Thus these antioxidants play important
role in day-to-day life by increasing the aging and reducing the cell destruction and cell damage.
These anti oxidants cannot be produced inside the body. They can be produced chemically by
taking the rich sources of Vitamin C and Vitamin E. These Anti oxidants are present in nature in
green vegetables. Vegetables and fruits are rich sources of Antioxidants.

Many experiments are conducted on mice because of the similarity of the genes around 99
percents. Experiments on mice with antioxidants have succeeded in increasing the life span of
the mice. The main reasons for the Aging are destruction of cells which is the death of the cell as
described in the free radical theory of aging and the other factors are like accumulation of DNA,
mutations that are being produced in the dna , loss of elasticity like hardening of tissues which
occur usually in the elder people. The best example for the accumulation of cell is Cancer, which
is due to accumulation of cells in larger quantity. The cells described here are the immortal cells
that never die that cause cancer
Mutations in DNA:
The mutation in DNA leads to the earlier aging in the small aged people. This is called as
Werner syndrome. In this syndrome we can observe that the young person at the age of twenty
will have the characteristics of the old person like the inability to walk, wrinkles showing up on
the skin, hardening of cells, organs and tissues like formation of Cataract in the eye. We can
observe these characteristics in the fruits like apple. If the apple is cut into two pieces and the
white part of the apple is made to expose to the outer world after some tome it is observed that
the color of the apple is changing into yellow color and the white part of the apple is becoming
harder.

Wear and Tear theory:

According to this theory the parts of the human body are compared with the parts of any machine
like car, which will be torn into different pieces after particular time period. The wearing is the
phenomenon observed at the time of the birth. The tear is the phenomenon that is observed
because of expose of the body to the chemicals, exposing to the pollution and the lack of good
exercises.

Acidification theory of aging:

The Acidification theory of aging relates to the aging phenomenon, which states that the loss of
acidic characters of the enzymes in the body leads to the slowing the aging process. The food
that is taken inside the body needs to be digested in order to get the energy to the cells. These
digestion process is controlled by enzymes .If the acidic nature is more then the aging process is
in normal condition and where as if there is any damage and that results in the loss of acidic
character in the body leads to the damage of the cells which leads to the speeding of the aging
process.

Cross-linking Theory:
This theory states that there is an adverse effect on the body because of the combination of
proteins and glucose. Exposing a protein to the glucose molecule in the presence of air that is
oxygen leads to the damage of proteins and this damage to the protein leads to fast aging. This is
clearly observed in the people with diabetes. Since the diabetes person has more glucose
concentration in the blood his proteins are damaged and the aging phenomenon is very fast in
this diabetes person. This ability decreases the resistivity of the white blood cells towards the
infection. The aging in the diabetes person is twice and thrice compared to that of non-diabetes
person. This decreases the cell growth and decreases the nutritional strength

Telomere Theory of Aging:

We know that the cell stops its division after a certain time because it can divide only a finite
number of times. A cell can divide only till 50 times and after the completion of fifty cell
divisions it leads to death of a cell. The question arises here about the cell division that how does
the cell know the divisions? Do they have any timekeepers to remind them the cell divisions…?
The answer is might be yes and the time Keepers are called as Telomeres.

Telomeres are called as cellular timekeepers, which are responsible for a finite number of cell
divisions inside the body. These telomeres are present in the cell attached to the chromosomes.
These telomeres are present on the both sides of the telomere. Each telomere has two
chromosomes. Since each chromosome has two telomeres there are 92 telomeres present in the
human body because of 46 chromosomes present in the human body. The quantity of the
chromosomes is not unique and it varies between species to species and organism to organism.
These telomeres are the sequences of nucleotides like A, G, T, C which are attached to the
sequences of DNA. These Telomeres are useful for identification and differentiation of
chromosomes. Each telomere is a hexes nucleotide containing 6 nucleotides. For each cell
division the length of the telomere will be decreasing and after a finite number of cell divisions
the length of the telomere will be shortened and it halts the cell division.

In the above graph you can see a green color sequence added to both the sides of chromosome.
This green color sequence is called as telomere, which is useful for differentiation among the
chromosomes. This Telomere is helpful in cell division. At the end of each cell division the
length of the telomere decreases gradually and after a finite number of divisions due to the
absence of cell division the division of cell is halted.
The halting of the cell division because of the absence of telomere is called as Senescence. In
order to protect the cell from cell from senescence and make the initiation of cell division an
enzyme is used which is used for cell division. This enzyme is called as Telomerase.

Telomerase:
Telomerase is an enzyme, which is useful for cell division. The DNA replication starts with dna
primer attaching to the opposite strands or nucleotides .The dna sequences will replace the
primers of the dna taking the direction from 3 prime to 5 prime. After the removal of final primer
the dna stops the replication. During the process of the dna replication this telomerase enzyme
donates its nucleotides to the telomere and again the replication of dna continues. There is limit
or final length for each telomere to stop the cell division. The minimal length of the telomere in
the human beings is 5 KB, which are 5-kilo base pairs. If the telomere decreases to the length of
5kb the cell division will be halted.

The telomere theory of aging is clearly observed in an organism called microfyalgia. This
microfyalgia is a uni cellular microorganism observed in dwell ponds. The uniqueness of this
organism is the presence of 40,000 telomeres. Since this organism contains only one cell, the
Senescence and telomerase activity is clearly observed in this microorganism. The telomerase
stabilizes the sequences by donating its nucleotides to the telomere. These telomeres cannot
completely avoid senescence and researches are still going on these telomeres in order to fight
against the cancer. The telomerase activity is found high in particularly some parts of the cells
like hair, epidemic cells like skin cells and also the cancer cells which are called as immortal
cells. This telomerase activity is weak in some parts of the body like somatic cells and
differentiates cells. In the somatic cells and differentiate cells the cell growth is very slow.

Telomerase is an enzyme, which is added to the DNA sequence to stabilize the sequence, and
this enzyme is a combination of nucleotides. Combination of six of the nucleotides results to
Telomerase. The sequences of this Telomerase may not same in entire human body. Sometimes
it may vary from chromosome to chromosome and it depends on the DNA sequences. These
Telomerase sequence will always depend on the length of the telomeres inside the body. The
nucleotides in the Telomerase enzyme will be the exact opposite to that of nucleotides of
telomere. For example if we consider a sequence of telomere as AAGGGT then the
corresponding telomerase enzyme sequence will be like TTCCCA. This opposite nucleotide
proportion is in order to describe the process of DNA replication. This telomerase enzyme is
helping during the process of DNA replication by donating the nucleotides.

Autoimmune theory of aging:

The Auto Immune Theory of aging states that ability of the reproduction of DNA increases
during the growth of the body, which is at birth, and it decreases during the aging .The immune
system is the major part of the body. The immune system is the defense part of the system, which
protects the body from foreign substances. During the aging process the DNA should be
reproduced correctly in equal intervals of time. As the aging process the ability to differentiate
between the proteins and antibodies should be high.

Redundant DNA Theory:

This Redundant DNA Theory is almost similar to that of a Wear and Tear theory and Auto
Immune Theory Of Aging. In this Redundant DNA theory the changes in the DNA and the
accumulation of DNA over the life time leads to the fastened Aging process

Reverse Aging Theory: l

Everyone would like to live a longer live without aging and without any physical destruction or
damage to the body and this cannot be possible because of accumulation of cells, death of cells,
mutations in DNA , losing of elasticity in the skin and tissues. The Reverse aging Theory deals
about slowing the process of living rather than stopping the aging. The aging process can be
slowed down by usage of chemical hormones in the body

Many manufactures say that increase of Hormones will slower the aging process and the
hormones increases the ability of fighting against the nutrition and increases the ability of white
blood cells towards the aging and increases the muscular strength. There are many dangerous
side effects on the human beings. Usage of this hormones lead to increase of feminine
characteristics in the human body which indirectly to damage of human man evolution

Caloric Restriction Theory:

Researchers say that aging process can be slowed down by the quantity of calories, decreasing
the amount of calories inside the body. They made these observations in the long living
organisms like ape, which take the fewer amounts of calories inside the body. We know that the
diabetes person is having lot of cholesterol inside the body and the amount of calories inside the
body is very high and because of these reasons the aging of a cholesterol affected person is very
high and it is almost twice or thrice to that of a normal person

Experiments were conducted on the mice for caloric restriction and it revealed the facts that by
restricting the amount of calories inside the mice increased the aging of the mice and the changes
have been noticed. These changes are like 10-20 percent negative because of some natural side
effects and 80-90% positive changes are observed because of caloric restriction. There are
several issues to this Caloric Restriction.

Issues:
 The issues are simple like aging and type of food we intake .The environmental conditions also
vary when compared to that of animals. Animals are not restricted to the food and environment
they live but the humans are social being whose environment is restricted. There are some other
differences like changes in the metabolic activity and the genes corresponding to the changes of
metabolic activity are also different in the human beings and monkeys. The digestive system and
the enzymes related to the digestion of food are not similar in both humans and animals.

The Aging theories that have been proposed have revealed the minor reasons behind the aging.
All the theories have discussed many common effects corresponding to the aging but there are
several unknown factors for aging. The above theories have revealed that smoking cigarettes and
drinking alcohol leads to the increase of the oxidants inside the body and the increase of the
amount of the oxidants fastens the aging process. According to the free radical theory of aging
the person who smoke cigarettes’ and consume alcohol die early due to the presence of increase
of free radicals but this theory fails in this case because on a observation it is found that an
American woman who has lived 125 years and who was dead recently used to smoke the
cigarettes and drink the alcohol even at the age of 120 years. There are many ways to slow the
aging which can be done taking good caloric food that are rich sources of Vitamin c, Vitamin d
and vitamin E.

Maintenance of good health condition:

Maintaining good physical fitness, which can be achieved by playing good games, can do this
and doing good physical exercises every day leads to a healthy and happy life. Decreasing the
amount of at food inside the body and taking low calorific food into the body because the large
amount of calories inside the body may decrease the process of aging. Having good physical
exercise in the body leads to good fitness and increase the metabolic activity inside the body and
this in turn increases the immunity power of the body and increases the immunity power of the
body.

Conclusion:
Aging process is an accidental process and inevitable process, which is necessary for the life.
Aging process cannot be stopped or changed. With out the aging phenomenon there is no
evolution and life.

References:

1)www.sciencedaily.com

2)www.wikipedia.org

3)mapping and cloning of human telomerase repressor gene on chromosome 3

4)www.anti-aging-today.org

5)”turning back the strands of time” American Scientist