The document discusses various models of aging at both the individual and non-individual level. It describes several key models including: mechanistic aging which focuses on damage at the cellular/DNA level; organismal aging which takes a holistic view of cellular aging effects; contextual aging which considers social/environmental factors; mouse models which are useful mammalian models; yeast models including replicative and chronological lifespan studies; cellular models which examine finite cell division capacity; and the decremental model which views decline as inevitable with age. The models provide insights into aging mechanisms but also have limitations in representing all species.

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Table of content
 Introduction
 Individual model
 Non individual model
 Selection of Model Sytem
 Mouse model of aging
 Decremental model of aging
 Yeast model of aging
 Cellularmodel of aging
 Characteristics model of aging

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MODELS OF AGING
AGING:-
The process of becoming older, a process that is genetically determined
and environmentally modulated.
Models of aging:-
The models are characteristerized in two models
1- Individual model
2- Non individual models.
1 - Individual Models:-
With individual models of aging, we focus on the individual person
. Mechanistic aging, sometimes referred to as the biological model, is broadly
defined as damage at the cellular level or DNA level results in accumulation of
mutations or incompetent cells.because biologists have focused on specifics in
different areas, like DNA, mitochondria, and free radicals.
Mechanistic aging states that as you get older your cells run into problems - maybe
as one was dividing the DNA got all jumbled, and now the cells that divided from
it don't work as well as before; or something got into the cell's mitochondria, which
helps power the cell, and damaged that. Now the cell is working on half the juice it
should. These accumulate and result in inefficient areas in the body, like the skin
not being as elastic or the heart growing weaker.
Organismalaging:-
is defined as a holistic view of an individual based on cellular
aging. With mechanistic, we look at the specific cells and how they work. With
organismal, we are seeing how they come together. So mechanistic is sort of

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subsumed by organismal because organismal focuses on the whole organism rather
than the individual parts.
One idea behind organismal aging is that there is a limit on the number of times a
cell can divide. Every organ is made up of cells, and many of them are repaired by
dividing cells. If they reach that limit, then they can no longer divide, and now the
organ is working with fewer and fewer cells. This is kind of like running a big fleet
of cars, and in the beginning you have 100 mechanics, and by the end, you have
one or two.
2-Non-Individual Models:-
Contextual aging:-
is defined as a description of a person's social and
environmental factors. This is you 'not acting your age.' Age doesn't necessarily
mean one has to act a certain way. However, society demands that people of a
certain age act a certain way.
Selection of model system:-
• Species lower on the phylogenetic scale, such as fish and mice, are effective
models for the study of basic mechanisms of aging .
• species commonly used for aging research, it is crucial to be aware of
physiological and behavioral differences associated with varying genetic
background, environment, and other factors to ensure appropriate model
selection.
Mouse model of Aging
Much has been learned from the study of aging in worms and flies, but it is
important to test the knowledge derived from these lower organisms in a
mammalian species. For this, the mouse is ideal. Not only does it have a relatively
short lifespan but, as a mammalian research model that shares 99% of its genes
with humans.

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Mice and rats are favorite subjects of scientists interested in human aging. Because
they are mammals, they are more closely related to us than yeast, flies, or worms,
and their relatively small size and short life span make them easier to study than
long-lived animals.
1-Metabolic Stability
The concept of metabolic stability was originally introduced in an analytic theory
of longevity to provide a molecular mechanism for the large variation in life span
observed between species. Metabolic stability, roughly speaking, describes the
capacity of the metabolic network to maintain steady-state values of redox couples
in response to random perturbations in the rates of enzymatic processes. The
significance of this concept in studies of aging resides in the metabolic stability-
longevity principle. This asserts that metabolic stability is the prime determinant of
the rate of aging and is positively correlated with the maximal life-span potential of
a species. Accordingly, strongly stable networks will be defined by slow rates of
aging, whereas weakly stable networks will be defined by rapid rates of aging.
Senescence is the result of spontaneous changes in the metabolic condition of the
cell during normal development. Studies consistent with are the empirical
investigations show that ATP/AMP ratio, a metabolic marker of stability,
decreases with age and that organisms with a larger ATP:AMP ratio live longer.
2-Calorie Restriction
Calorie Restriction increases longevity by increasing the metabolic stability of the
regulatory networks. We can therefore infer that, in the case of humans, a species
close to the condition of maximal metabolic stability, DR will have negligible
effect on stability, and hence no effect on maximum life span. However, DR may
have an effect on mean life span. Mean life span is simply a measure of our ability
to minimize premature death. DR (Dietary Restriction) can influence mean life
span by simply reducing the incidence of diseases suchas diabetes, atherosclerosis,
and hypertension. These changes, however, will result in an increase in life span of
only about 3–5 years—a moderate effect. Since DR will have a negligible effect on
metabolic stability, it will exert no effect on the rate of aging and hence induce no
changes in the human senescence process.
3-Oxidation Stress

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In mice, interventions that enhance oxidative damage generally shorten lifespan
metabolic activities that sustain life also create “metabolic stress,” which, over
time, results in damage to our bodies. Take breathing—obviously, we could not
survive without oxygen, but oxygen is a catalyst for much of the damage
associated with aging because of the way it is metabolized inside our cells. Tiny
parts of the cell, called mitochondria, use oxygen to convert food into energy.
While mitochondria are extremely efficient in doing this, they produce potentially
harmful by-products called oxygen free radicals. The accumulation of oxidative
(free radical) damage in our cells and tissues over time might be responsible for
many of the changes we associate with aging. Free radicals are already implicated
in many disorders linked with advancing age, including cancer, atherosclerosis,
cataracts, and neurodegeneration.
4-Mutations
Mutations that extend lifespan are likely to affect the rate of aging, while those that
reduce lifespan either alter aging or increase the risk or severity of a particular
disease. According to Mouse Genome Informatics 301 mutations decrease survival
by causing or promoting susceptibility to disease and 46 promote features of
premature aging. In Table we list genes whose mutations decrease longevity and
appear to alter aging. The roles of these genes, similar to the mutations that extend
longevity, suggest that maintaining DNA stability and antioxidative stress are
important molecular mechanisms that regulate aging and longevity. For example, a
knockout of Bub1b induces chromosome (Chr1) instability, reduced expression of
PolgA increases mutations in mitochondrial DNA, and knockouts of Msra and
Prdx1 increase oxidative stress.

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The growing interest in mouse aging and genetics has been strongly stimulated by
the sequencing of the mouse and human genomes and by the realization that most
human genetic diseases can be modeled by changes in equivalent genes in these
rodents. The fact that aging can be slowed by dietary or genetic changes in mice is
fueling new enthusiasm for the use of this model mammal as a guide to human
aging
Decremental model of aging:
• Many of our attitudes about aging are based on a decremental model of
aging, which holds that progressive physical and mental decline is inevitable with
age. In other words, chronological age is what makes people “old.
Attitude towards aging:
 The prevalence of the decremental view in our society can be explained in
part by ignorance and a lack of contact with older people.
 The result is a climate of prejudice against the old.
 A researcher coined the word ageism to refer to this prejudice.
 Young people tend to believe that the old suffer from poor health, live in
poverty, and are frequent victims of crime. Such beliefs, however, affect
stereotypes of the elderly.
Changes in health:
 Most people over 65 are in reasonably good health; of course, physical
strength and the senses do decline.
 About 40 percent of the elderly have at least one chronic disease.
 The quality of health care for the elderly remains by and large inferior to that
of the general population.

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Changes in life situation:
For younger people, transitions in life–graduation, marriage, parenthood–are
usually positive and create a deeper involvement
In late adulthood, transitions–retirement, widowhood–are often negative and
reduce responsibilities and increase isolation.
The symptoms of depression are very common in older adults. On the positive
side, older people continue to learn and develop skills more than ever before.
Changes in mental functioning:
As people age, there are also changes in many of the mental functions they use,
although there is much less decline in intelligence and memory than people think.
John Horn (1982) has proposed two types of intelligence:
Crystallized intelligence–the ability to use accumulated knowledge and learning in
appropriate situation.
Fluid intelligence–the ability to solve abstract relational problems and to generate
new hypothesis.
Senile dementia:
A small percentage of people develop senile dementia in old age. Senile dementia
is a collective term that describes conditions characterized by memory loss,
forgetfulness, disorientation of time and place, a decline in the ability to think,
impaired attention, altered personality, and difficulties in relating to others.
Alzheimers disease:
The most common form of senile dementia is Alzheimer’s disease Alzheimer’s
disease is an affliction more commonly seen among the elderly. Alzheimer’s is a
neurological disease marked by a gradual deterioration of cognitive functioning.
The causes of Alzheimer’s are complex and still not completely understood.
 Genetic susceptibility plays a role.

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 At present there is no cure.
Cellular model of aging:
Cellular aging is the decrease in the cell's ability to
proliferate with the passing of time. Each cell is programmed for a certain number
of cell divisions and at the end of that time proliferation halts. The cell enters a
quiescent state after which it experiences CELL DEATH via the process of
APOPTOSIS.
Factors effecting in aging process and functional relationship between them:
Hallmarks:
Genomic instability, telomere attrition, epigenetic alterations,
loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction,
cellular senescence, stem cell exhaustion and altered intercellular communication.
At cellular levels, age-dependent declines can arise from the accumulation of
damage and erosion to cellular macromolecules including proteins, RNA and
DNA, usually a result of cellular stress and environmental insults.
Of these, DNA damage accrual and insufficient DNA repair often accompanied by
oxidative stress and mitochondrial dysfunction is a principal factor contributing to
cell senescence and aging.

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Conversely, DNA repair pathways delay cell senescence and aging by
maintaining genomic integrity.
Telomerase theory of aging:
• Telomeres are…
Repetitive DNA sequences at the ends of all human
chromosomes.They contain thousands of repeats of the six-nucleotide sequence,
TTAGGG .In humans there are 46 chromosomes and thus 92 telomeres (one at
each end) .Senescent cells have shorter telomeres .length differs between species
.In humans 8-14kb long .Telomere replication occurs late in the cell cycle.
Once the telomere shrinks to a certain level, the cell can no longer
divide. Its metabolism slows down, it ages, and dies. Telomerase (enzyme that
extends telomere) works by adding back telomeric DNA to the ends of
chromosomes, thus compensating for the loss of telomeres that normally occurs as
cells divide. Most normal cells do not have this enzyme and thus they lose
telomeres with each division. Shorter telomeres have a negative effect on our
health.
Telomere shortening is the main cause of age-related break down of our
cells.When telomeres get too short, our cells can no longer reproduce, which
causes our tissues to degenerate and eventually die. Some cells, like those found in
the skin, hair and immune system, are most affected by telomere shortening
because they reproduce more often
Yeast Model system of aging
The budding yeast Saccharomyces cerevisiae is a widely used model of cellular
and organismal aging. The first studies of yeast aging were published over 50 years
ago, in which yeast cells were shown to have a finite replicative capacity
Replicative life span was thus defined as the number of daughter cells produced by
a mother cell before senescence. A second model of aging has more recently been
developed in yeast, termed chronological aging. In contrast to replicative life span
(RLS), chronological life span (CLS) is defined as the length of time a yeast cell
can survive in a no dividing state. These two models for aging in yeast provide a

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unique opportunity to compare and contrast the aging processes of both
proliferating and nonproliferation cells in a simple single-celled organism
The two lifespans of yeast. The metric of replicative lifespan is the number of
mitotic divisions a mother cell (M) undergoes before senescence, this being also
the number of daughter cells (D) that it produces. The metric of chronological
lifespan is the length of time that a stationary phase cell remains viable under
defined conditions of maintenance, viability being measured as its capacity to re-
enter the mitotic cell cycle when supplied with nutrients.

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Ageing and longevity
‘Ageing’ is a process — a functional decline that is essentially a by-product of
natural selection operating to achieve the optimal balance of the available
resources between the competing priorities of somatic maintenance and
reproduction. ‘Longevity’, in contrast, is a parameter — the length of time that
individuals will remain alive in the absence of death from extrinsic causes, this
being inversely proportional to the pace at which ageing occurs. ‘Ageing’ and
‘longevity’ are terms that are frequently used interchangeably.
Apoptosis and oxidative stress
Yeast apoptosis and aging remains correlative, but highly intriguing. Both
replicative and chronologically aged cells show markers consistent with apoptotic
death . At present, however, it remains unclear whether there exists a causal
relationship between apoptosis and senescence in yeast. It has been reported that
deletion of the yeast caspase YCA1 results in an increase in chronological
longevity, but only after the culture falls below 10% viability. This suggests that
apoptosis exerts an effect on longevity only after the majority of cells have already
undergone senescence. Thus, for most cells in the population, activation of the
apoptosis-like pathway may be a response to the damage leading to senescence.
The observation that apoptotic markers are present in both replicative and
chronologically senescent cells may be an indication that the ultimate cause of
senescence is similar in both dividing and nondividing yeast cells. This would be
consistent with the finding that chronologically aged cells have a reduced RLS and
that some interventions (e.g., DR or reduced target-of-rapamycin (TOR) signaling)
increase both RLS and CLS.
Characteristics of model organism
Model organisms are usually chosen for reasons of convenience. Depending on the
type of research performed, common characteristics tend to include:
 Small Size

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 Rapid Generation Time
 Easy Upkeep
 Easy Experimentation: in genetics, and ideal model organism is
transformable, there are techniques to isolate nucleic acids, etc.
 High Volume of Background Information
Disadvantages of model organism
The general disadvantages are:
1. Your model may not be truly representative of similar species. Example- Plant
geneticists use Arabidopsis thaliana as a model, however as plants go Arabidopsis
has an abnormally small genome, and comparatively little repetitive DNA.
2. Genetic Variance. When doing certain types of studies your data might vary
because there is natural genetic variance in a population. This can be overcome by
using inbred lines that have low genetic variability which can make your results
more consistent.
3. Background Knowledge. It's not always possible to use a model that has
extensive background information. Many genomes have been sequenced. If you
use a model that has not been sequenced you are limited as to what types of
experiments you can do (or you are forced to do extensive preliminary
experiments).
4. Transfer of Methodology. Techniques used in your model may only work in
your model and will not work in other species. This also includes applications like
statistics.
5. Lack of Methodology. You may wish to perform certain types of experiments,
however it may not be possible. For example efficient targeted gene removal is
currently not possible in plants. To properly characterize a gene you should look at
a null mutant, however this is not always possible.