What is an Aging? Describe various theories related to aging?

It is defined as a disorder in which there is a change in the biology of organism. It is also known as the senescence. After the maturity it ages and such changes range from single cell to multiple cell in their function and other features. There are multiple theories which explain the sequence of ageing. This process is mainly controlled by the expression of gene which changes and leads to accumulation of changes by the biological process. The senescence is also known as the senex which is Latin word. It means ageing or old age or advanced age.

What is a Cellular senescence?
It is defined as a disorder in which there is a normal diploid cell. It does not have the ability to divide after the multiple divisions in vitro. There are few cells which become aged and there are other cells which do not. The ageing of few cells is caused due to the breakdown of double replicated DNA, toxins. They become aged after few replicating cycles. This process is known as the replicative senescence. It is also known as Hay flick phenomena. It is also known as the Hay flick limit in honor of Dr. Leonard. In the year 1965, first publication was printed about this matter. If there is damage to the DNA cells have the ability either to damage or self destruct themselves and include the short telomeres and apoptosis. It occurs if the damage is irreparable. In the case of cellular suicide one may see the death of one or more cells which may give benefit to the organism. In the plants where there is a death of the water conducting cells which are known as the xylem. One can look for the trachieds and vessels. It allows the cell to function better and supply the water to upper parts of a plant.

What is an Aging of the whole organism?
It is defined as a disorder in which there is a senescence of the organism. Aging is defined as a process in which the individual loses the ability to cope stress and an increase in the homeostatic balance along with the increased risk of aging associated disease. The final destination of the aging is death. Old age is not considered to be the cause of death as there is always other cause associated with it like the cancer, disease of heart, liver and lung. The rate of aging is different in the different individuals. It is more in tortoise as compared to other species. These differences are inherited. For example, the mouse gets elder when he is 3 year old but in case of human it takes more than 80 years. There are many physiological processes which are affected by the differences in genetics. It includes the DNA repair efficiency, anti oxidant enzymes and the rate of free radical production.

The law of mortality arises from the senescence of organism. It is known as the G M Law of mortality. It states that the mortality rate is directly proportional to the age. There are certain reptiles and fishes which age slowly. It is known as the negligible senescence. They have very long life spans. A few of them may also have a negative senescence which means that the mortality rate is inversely proportional to the age. It does not support the G M Law of mortality.

The replicative aging may or may not play a crucial role in the process of aging of organism. It must be included in the active area of investigation.

What are the theories of aging?
The process of aging is not simple. It may occur from the different mechanisms. It can exist due to number of reasons. It is not universal in the occurrence and there are evidence which suggests that the cellular aging occur in few species. It does not allow the spread of cancer. There are few species in which the aging is next to nothing and is difficult to detect. In this case there is an absence of the post mitotic cells. They decrease the effect of causing damage to free radicals which occur with the help of division of cell and dilution. These species are not immortal and they die due to the disease or trauma later in life. The different species has different life spans. It gives an idea that the environmental and genetic factors play a crucial role in the process of aging. There are traditional theories which have explained the aging and have divided the theories of aging into programmed and stochastic theory. The programmed theories play a crucial role in the aging which is controlled by the biological clock which hardly stops. The regulation depends on the changes in expression of gene. It involves the system which helps in the repair, maintenance and defense mechanism. The stochastic theory is linked with the impact of environment on living organisms. It causes the cumulative damage as a result of aging. It results in the injury to DNA, cells. It occurs with the help of oxygen radicals and cross linking which act as anti oxidants.

The failure of hemodynamic is known as ageing and involves the genes which help in the maintenance and repair. The molecular damage occurs due to the stochastic events and also due to the molecular heterogeneity. The chances of death are determined by the chance events. The hemodynamic systems are made up of complex and inter acting systems. It occurs in the biological system. The decrease in the size of hemo dynamics is known as ageing. It occurs due to the molecular heterogeneity.

3.1 What are Evolutionary theories of aging?
It includes the gene which can be expressed at many stages. So, a natural selection can lead to the harmful and lethal alleles. It occurs after the process of reproduction. It may lead to the aging. Due to increase in the smaller probability of the organism aging can occur. At older age the organism is still alive and leads to the predation and accidents. They are random and are not dependent on the age. There are certain strategies which can result in the higher rate of reproduction which occurs at a young age. The overall life span is not so long. It results in a lifelong process of reproduction which can lead to the natural selection. Ageing is a result of investing sources in the reproduction. It is the maintenance of the body. The organisms are killed by the predation, accident and disease. It does not bother how much energy is needed to repair the body. There are other theories of ageing which do exist and are not exclusive in it.

There was a geneticist J B S Haldane who tried to figure out the reason why the mutation which causes this disease was in the population and not the natural selection was removed. The disease starts at the age of 45 and is neurological in the function. It becomes fatal within 10 to 20 years. The geneticist J B S Haldane thought that the dominant mutation can lead to the human pre history which survived up till the age of 45. In the older age few were able to survive. Their contribution to the next generation was not much. The small relatives to the large groups of the younger group faced a selection against the late acting mutations which were quite small. If a young individual is involved in the mutation one can go for a selection against the individual. It will be a strong case. The accumulation in the population is mainly of late acting hazardous mutations. It occurs by the genetic drift over a evolution time. It has been proved experimentally. Mainly, these defects lead to the age related mortality.

The P Medawar used the observation in the mutation accumulation of the theory of aging. The natural selection must be weakened by the increase in age. It happens even in the theoretical population which does not die. If it is exposed to the real hazards than the predation, disease and accident can occur. The immortal population whose fertility does not decreases with the time. So, there are few individuals which are alive in the older age group. It is referred as the extrinsic mortality. There are young cohorts which are not decreased by the number but by the extrinsic mortality they contribute a lot to the next generation. Than the few remaining cohorts which are old and the force of selection is done against the late acting deleterious mutations. It involves the few individuals which are weak. The mutations cannot be a selected against and they may spread over the evolutionary time in population.

The prediction made by this model is that the species with high extrinsic mortality in nature will have more age and have a shorter life span. It is borne out among mammals with a well studied term in times of history and other features. One can find the co relation between the size and life span of mammals and its figure that the larger species live longer than the smaller species. It occurs in the controlled environment or under optimum conditions. One can also have some exceptions too. In case of bats and rodents they are of similar size but they have a different life span. Bats live longer than the rodents. The little brown bat is of small size as compared to the mouse. It can live longer than the wild variety. A mouse has the ability to live for more than the 2 to 3 years even if the conditions are optimum. This can be explaining by the fact that the bat has very few predators and so the rate of extrinsic mortality is low. There are more individuals which can survive longer than the later age. So, the force of selection against the deleterious effect is very large. There are less late acting deleterious mutations which can lead to the slowing of aging process and a longer life span. Birds are warm blooded and have a similar size like the small mammals. They are able to live 5 to 10 times as long as compared to other species. They have less predation pressures like the diseases etc. and are safer as compared to the ground dwelling mammals. The fewest predators are present in the case of sea birds. They live the most.

One should compare the size of organism with the life span. The mammals which predate have a long life span and prey the animals in a controlled manner. It includes the zoo or natural reserves. The life long span of primate can be explained by the body size along with their intelligence and ability to socialize with the other animals. Their smart and working together ability make them less prone to the predator.

There was other evolution theory which was proposed by the G C Williams. It included the antagonistic pleiotropy. There is a single gene which can affect the multiple traits. There are few traits that can increase the fitness early in life. It may have negative effects in the later part of life. More individuals are alive at the younger age as compared to the older age and one can select the small positive effects early in the life. One can select the negative effects later on weakly. This author also suggested that the gene code for the deposition of calcium in bones can increase the survival in the juvenile stage. It is promoted by the natural selection. This gene also helps in the deposition of calcium in arteries. It may lead to the side effects in old age. It may lead to the natural selection of pleiotropic gene which provides a good effect in the young life. Fitness is comparatively good in the case when the fisher’s reproduction value is high. It can be low as the fisher’s reproduction value is low.

3.2 What is a Gene regulation of aging?
It includes the multiple genetic components which are identified by the other organisms. It includes the simple budding yeast and S Cerveisiae. It also includes the worms and fruit flies. The couple of conserved aging pathways have been discovered with the help of study of these organisms.
One of the pathways includes the gene SIR2 which is a NAD dependent. It is histone de acetylase. The gene SIR2 is required to silence the genome at three different loci. It includes the yeast mating loci, telomeres and the DNA of ribosome. There are few species of yeast in which the process of aging can occur due to the homologous recombination between the DNA of ribosome. The extra chromosomal ribosomal DNA is referred as the ERCs and is formed due to the excision of ribosomal DNA. The extra chromosomal ribosomal DNA is referred as the ERCs divide and combine with the mother cell during the division. They cause the aging of cell by removing the important nuclear factors. The extra chromosomal ribosomal DNA is referred as the ERCs are not found in other species of yeast. They play a role in the replicative aging. The extra chromosomal ribosomal DNA is referred as the ERCs do not play a role in the aging process in the humans. They do not aggregate in the humans as seen in the yeast. The worms, flies and humans have the extra chromosomal circular DNA is referred as the ecc DNA. The role of extra chromosomal circular DNA is referred as the ecc DNA is controversial.

There is no connection between the extra chromosomal circular DNA is referred as the ecc DNA and aging in humans. There are extra copies of the SIR 2 gene which have the ability to extend the life span of worms and flies mainly. The role of extra chromosomal circular DNA is referred as the ecc DNA in worms is controversial. The homologous of SIR 2 in higher organisms do not play an important role in the life span of higher organism. There is a protein present in the human who is known as SIRT 1 and has the ability to de acetylate p 53 and ku 70. It also includes the fork head family of factors of the transcription. Acetylates can be regulated by the protein which is known as SIRT 1. It mainly acts on the histone residues like de acetylate.

The aging in yeast is affected by the RAS 1 and RAS 2. They have a homologue of the human. The life span in yeast is increased by the RAS 2 over expression. The life span in yeast is also regulated by the resistance to oxidative stress. There is a protein known as the super oxide dis mutase and it provides a good effect against the free radicals of mitochondria. It can increase the life span of yeast and it occurs in the stationary phase at the time it is over expressed.

The process of aging in the human is regulated by the insulin or IGF 1 pathway. There are few mutations which affect the insulin like signaling mainly in the worms. There is a growth hormone axis which is linked to the more life span. The SIR 2 activity in the yeast is controlled by the nicotinamidase PNC 1. Its transcription is controlled by the up regulation which can occur under the stressful conditions. It includes the different types of shock like osmotic, heat and restriction in the calorie intake. It has the ability to change nicotinamide to niacin. It affects the activity of SIR 2. The nicotinamide which is found in the humans is referred as the PBEF. It has a quite same function and the nicotinamide which is found in the humans is referred as the PBEF has a secreted form of visfatin. It helps to control the serum insulin levels. It is controversial whether these steps are present in the human or not. There are many differences between the biology of human and model organisms.

The activity of SIR 2 Increases the restriction of calorie. These occur due to the absence of glucose in the cells. More NAD is available and it can activate the SIR 2. The skins of red grapes contain reseveratol which is a poly phenol. It increases the life span of yeast and worm. It also shows an activation of the SIR 2 and is quite similar to the restriction of calorie. So, we can say that the restriction of calorie depends on the SIR 2.
The expression of gene is not controlled properly. The random changes in the expression levels of gene lead to the process of ageing. It is due to the study of many genes in yeast. There are single cells which are quite like and have a different response to the outside stimuli. They have different life spans. It shows that the epigenetic factors play an important role in the expression of gene as well as aging along with the genetic factors.

There are number of genes which are linked to the longevity. In this there are researches which are done on the model organisms. It includes the filamentous fungi, baker yeast and the round worm present in the soil. It includes the fruit fly along with mouse.

3.3 What is a Cellular senescence of aging?
It includes the aging which is not universal in the presence. It is absent in the single celled organisms and reproduces through the process of mitosis. There are many organisms which do not show the cellular aging in perennial plants, sponges and corals. It also includes the lobsters. There are certain species of the organism which show cellular aging and they become post mitotic. They do not divide by the process of cellular mitosis. The cells undergo replicative senescence. The cells which become post mitotic in certain species is not controversial. It is a matter of the research and a lot of speculation. It is known that the cellular aging became a way to prevent the cancerous condition. There are somatic cells which have the power to divide lot of times can aggregate the mutations of DNA. If the division of cell continues the chances of it becoming cancerous are more.

The telomeres also play a crucial role in the cellular aging. It has become popular as the adverse effects of the cloning have been established. The cloning can also change the shortening of telomeres. The number of divisons has been limited by the shortening of telomeres of chromosome. It occurs with each cycle. It also leads to the process of aging. There are few cells which do not age and have immortal life. It is need to known that what allow these cells to and their occurrence is due to the shortening of telomeres or their division is still not clear. It is quite possible to genetically alter other cells and have a same capability. It is also known that it is possible to genetically alter the cells so that they have a same capability. It is also known that the cells can be genetically engineered so that they can have the capability to act in a human body. It is also known that the gene therapy can employ a gene therapy and can stop or reverse the process of aging. It makes the organism immortal.

Mostly, cancer cells are immortal. The evasion of cellular senescence can lead to the most of tumors. It activates the telomerase genes. It also suggests that the reactivation of telomerase in the healthy individuals can lead to the increased risk of cancer. The role of cell senescence in the aging of organism is not known. It is not the active areas of investigation. There are certain mice which do not have a telomerase and do not show fast aging process.

3.4 What is a Chemical damage of aging?
It includes the early aging theories. It includes the rate of living hypothesis by the R Pearl in the year 1928. It was based on the work done by M Rubner. It states that the increase in metabolic rate leads to the short but maximum life span. In the different types of specific damage there is an idea which states that the byproducts of the metabolism can lead to the other things which are equal. This is the common theory that the fast metabolism can lead to decrease in the life span. This theory fails to explain the differences in the life span either within or different species. There are few calorie restricted animals which can lead to the increase in calories per gram of body mass. It acts as an ad libitum counterpart. It has a longer life span. The life span of birds is not detected by the poor metabolic rate. It is not a good predictor. It is quite similar in the bat and other species. They have decrease in the mortality rate due to the predation. They have a long life span even if the metabolic rate is quite high. In the recent studies it has come to known that there are few modern statistical methods to correct the effects of body size. It also helps in the phylogeny. It also states that there is no correlation between the metabolic rate and longevity of mammals or birds.

In respect to the chemical damage one has to look for a metabolism. The injury to long lived polymers can cause a change in the structural protein. It also includes the DNA. It is caused by the presence of chemical agents in the body like the oxygen and sugars. They may lead to the process of aging. The breakdown of bio polymer chains can cause the damage by a cross linking of the bio polymers. In this one can see a chemical attachment of haptens to the bio polymers. The haptens are unnatural substituents.

In the aerobic conditions little bit oxygen is metabolized by the mitochondria. It is changed to the super oxide ion. It can be changed to hydrogen per oxide. There is a formation of hydroxyl radical along with the per oxides and singlet oxygen. It has the ability to liberate free radicals which can cause injury to the proteins and DNA. There are few metal ions which are formed inside the body. It includes mainly the copper and iron. They can participate in the process. There is a hereditary effect known as Wilson’s disease in which there is a large amount of copper stored in the body. The symptoms resemble an accelerated senescence. These processes are termed as an oxidative damage which are linked to the benefits of nutritionally derived poly phenol anti oxidants.

There are few sugars like glucose, fructose which are used to and can react with few amino acids and lead to the production of sugar adducts. It can act with the lysine and arginine. It also has certain DNA bases which can form sugar adduct. This process is referred as the glycation. They can arrange themselves to form a reactive species which have the ability to cross link with the structural proteins or DNA. It has same bio polymers and other proteins which are non structural. The people with diabetes have an increase in the level of blood sugar which is quite helpful in the cases of ageing associated disorder. They occur much earlier than the other population. One can delay the disorder with a rigorous control of blood glucose levels. One suggests that the damage to sugar is linked to oxidant damage in a process known as the glycol oxidation.
There are free radicals which are linked to the injury to DNA, proteins as well as lipids. The injury to protein mainly occurs by the glycation. The injured protein and lipids get accumulated in the lysosomes as lipo fuschin. The loss of function can occur due to the chemical injury to structural protein. An injury to the collagen of blood vessels may lead to the vessel wall stiffness. It may lead to the hyper tension. The thickening of vessel wall and the formation of reactive tissue leads to the process of atherosclerosis. It is quite similar in the kidneys and lead to the failure of kidney. The cellular functionality is reduced by the damage to enzymes. The inner mitochondria membrane goes into the per oxidation of lipids. It decreases the electric potential and has the ability to generate energy. There is no co incidence that the accelerated aging disease which occur due to defective repair of DNA enzyme. It is known that the effect of alcohol on aging is explained by the activation of hypo thalamus pituitary axis. It occurs with the help of alcohol. It also activates the glucocorticoid secretion. Its long term exposure to the alcohol increases the process of aging.

3.5 What is a Reliability theory of aging?
It includes the biological systems which start their adult life. It leads to a large amount of damage. It is mainly a common theory which tells us about the failure of system. It also tells us about the researchers to have a look for the failures which are related to the age. It forms a reliable structure which can be reliable too. This theory also tells us about the systems that are made up of non aging elements. They have a good failure rate and have ability to fail more as compared to the other systems. It happens with the age. This system is present in the elements which cannot be replaced. The systems ultimately lead to the process of aging.

The late life mortality deceleration also helps to know about the leveling off. It tells about the late life plateau of mortality. It is a consequence of the exhaustion of redundancy. It occurs in very old ages. It also explains the increase in mortality rate with age. It is referred as the Gompertz law. It occurs in many species. It takes into the view into the defects in newly formed systems. It also tells why the organism is died according to the Gompertz law. There are technical devices which do not work according to the power law. It is referred as the Weibull law. This theory also tells us about the conditions which can allow the organism to die. It is in relation with the power law which is referred as the Weibull law. The organism must not have any initial flaws and must be free of the defects. This theory also helps us to find a failure law which is indicated to old as well as young people. The general failure law has special cases in the form of power law which is referred as the Weibull law and Gompertz law. This theory also tells us about the contrasting features between the mortality rates of population within a species. It decreases with the age. It is referred as the compensation law of mortality. One can observe the convergence of mortality as the initial differences are removed due to the redundancy levels.

In the recent studies an early aging has been observed in the cases of few organisms and it has been possible due to the failed outcome of early experiments related to the cloning. This issue came into the light in case of dolly ship. She died from a contagious lung disease. There is a controversy regarding the dolly ship that she may have died due to the early aging. Dr. I Wilmut was the one who created the dolly ship and he contributed her death due to the unrelated facts that she was a clone. There are other sets of hereditary diseases in which there is a disease known as progeria. It is known for some time. It is a genetic problem. The patients who exhibit the symptoms include the fast aging along with a skin which has wrinkles. In the journal nature one saw a Gilford progeria syndrome in the year 2003. It was published in the month of May. It gave a clue regarding the damage to DNA and not the oxidative stress. It leads to increase in the process of aging.