2. AGEING
Ageing is a progressive accumulation of changes
with time, associated with the deterioration of structure
and function and is responsible for the ever increasing
susceptibility to diseases and mortality and
impaired reproductive capacity.
Components of aging are biologic, statistical and
Phenotypical.
Senescence: process of aging of cell at the
organism level.
3. CHARACTERISTICS OF
SENESCENCE
It is an universal process
The changes come from the organism itself
The process occurs slowly
The process contributes to deficit
4. BIOLOGICAL AGEING
Biological aging, senescence, is the process of change in the
organism, which over time lowers the probability of survival and
reduces the physiological capacity for self-regulation, repair and
adaptation to environmental demands”
Has 3 types:
Primary aging: is the basic, shared, inevitable set of gains or declines
governed by some kind of maturational process
Secondary aging: is the product of environmental influences, health
habits, or disease and is neither inevitable nor shared by all adults
Tertiary aging: refers to quick deficit in the last few years prior to
death
5.
6. THEORIES OF AGING
PROGRAMMED AGING RANDOM EVENTS
GENETIC LIFE SPAN
GENETIC PREDISPOSITION
THEORY
TELOMERE THEORY
SPECIFIC SYSTEM THEORIES
WEAR AND TEAR THEORY
RATE OF LIVING THEORY
WASTE PRODUCT
ACCUMULATION THEORY
CROSS LINKING THEORY
FREE RADICAL THEORY
AUTOIMMUNE THEORY
ERROR THEORIES
ORDER TO DISORDER THEORY
7. PROGRAMMED AGEING
THEORY
It says that aging and death are genetically
determined and are “programmed” in all
organisms.
Life expectancies are seen as
pre programmed within a species-specific
range.
8. GENETIC LIFE SPAN THEORY
The length of life is genetically programmed
It is said by the theory that an organism’s life span is part of genetic
makeup
9. DISPOSABLE SOMA THEORY
Evolution selects strategies that prioritise the utilisation of FINITE
resources to maintain germ cells necessary for reproduction rather
than the soma cells or the non germ cells, hence age related
accumulation of damage to the soma occurs.
10. GRANDMOTHER EFFECT
Another theory of evolution says in case of humans the care is
provide to the offspring by their long lived grandmothers. This also
explains the development of an unusually long post reproductive
period of life in humans.
11. TELOMERE THEORY
Telomere:
It is the tail of chromosome that has no genetic information and
contains redundant TTAGGG sequence repeated several times.
Telomeres protect the ends of chromosomes from being degraded
and fusing with other chromosome ends.
Telomere theory is based on the fact that everytime a cell replicates,
it loses a part of its telomere
The older the cell, the more time it has divided, the shorter the length
of telomeres
As the length of a telomere decreases, changes may occur in patterns
of gene expression that could affect both the functioning of the cell
and the organ system in which it operates.
12.
13. EPIGENETICS ALTERATIONS
Multiple systems regulate the gene expression,
such as.. DNA methylation, histone modification,
chromatin remodelling. All these processes
change with age and there is altered
transcription of these genes and thus changes
of ageing are found .
The EPIGENETIC CLOCK is a consistent age related pattern of DNA
methylation changes in human blood sample that reflect the
chronological age of the individual.
Sirtuins regulate the histones through deacetylation and thus alters
the life span , eg. RESVERATROL increases the life span in some
model organisms.
14. METABOLIC THEORY
(CALORIC RESTRICTION)
It proposes that all organisms have finite amount of metabolic lifetime and
that organisms with a higher metabolic rate have shorter life span.
Caloric restriction is defined as approximately 30% reduction of calorie intake
without malnutrition.
Research on rodents, dogs, monkeys have demonstrated that caloric
restriction increases the life span and delays onset of age dependent diseases.
15. The key nutrient sensing pathways include...
Insulin and IGF 1 signalling pathways: downregulation of this
pathway leads to longer life. Humans with Laron syndrome (GH
Receptor Deficiency) have lesser risk of developing cancer and
diabetes
mTOR pathway: this pathway is activated by insulin/IGF 1
signaling pathway and amino acid and thus can be manipulated
by dietary protein intake.
Sirtuins: they are activated in response to low energy supply.
Increased sirtuin activity is associated with increased life span.
AMP activated Protein Kinase (AMPK): Dietary restriction causes
increase in AMP which again triggers the activation of AMPK
which is associated with increased life span.
Fibrobalst Growth Factor 21 (FGF21): Dietary protein restriction
causes increased FGF 21 which in turn activates the IGF1 and
the AMPK pathway and thus increases the life span.
16. NEUROENDOCRINE THEORY
Developed by Vladimir Dilman, the neuroendocrine theory of aging
states that “The effectiveness of the body's homeostatic adjustments
declines with aging—leading to the failure of adaptive mechanisms,
aging, and death.” This theory has also been referred to as the aging
clock theory and the pacemaker theory.
Focus changes in the hypothalamus and pituitary gland that lead to
decreased function of the endocrine system and widespread aging
effect.
17. RANDOM EVENT THEORIES
WEAR AND TEAR THEORY:
Suggest that the body is much like a machine
The human body “wears out” over time due to the stresses
Some kinds of exertion or activity promote vitality and are essential
to long life
Other kinds of stressful activities are detrimental to longevity (tears)
18. FREE RADICAL THEORY
Free radicals are by products of metabolism can increase as a result
of environmental pollutants.
When they accumulate, they damage the cell membrane, decreasing
its efficacy
19. CELLULAR AGEING
First described by Hayflick and Moorehead in 1961.
They showed human cells in culture do not divide infinitely but up to
a certain limit (Hayflick limit) after which they do not replicate.
Thought to be associated with :
•Ability to respond to stress decline
•Homeostasis imbalance occurs
•Progressive deterioration of structural properties
•Decrease in functional efficacy of cell
•Reduced power of repair and regenaration
20. IMMUNE SENESCENCE
Immune senescence : age related functional diminution of the
immune system.
Lower rate of T lymphocytes (killer cell) proliferation in response to a
stimulus and therefore a decrease in body’s defence against foreign
pathogen.
Also there is thymic involution with reduced naïve T cells, impaired
memory cells.
Changes include:
Decreased resistance to tumour cell challenge and the development
of cancer
Decreased ability to initiate immune process and mobilize defences in
aggressively attaching pathogens
21. MITOCHONDRIAL
DYSFUNCTION
•Age related changes in the mitochondria causes impaired Complex
IV activity and thus increased electron leakage and decreased ATP
production.
•Mitochondrial DNA is susceptible to free radical damage due to its
close proximity with these agents during oxidative phosphorylation
and lack of histones and repair mechanisms in these organelles.
22. LOSS OF PROTEOSTASIS:
With aging, the processes of removal of damaged proteins from cell
by autophagy and lysosomal systems, as well as ubiquitin
proteosome system lead to formation of intracellular and extracellular
aggregates (lipofuschin, amylin)
AMYLIN
LIPOFUSCHIN
23. STEM CELL EXHAUSTION
The age related reduction in the number of stem cells is probably due
to replicative senescence and telomere shortening.
24. ALTERED INTERCELLULAR
COMMUNICATION
Aging also is associated with low grade innate immunity activation
which causes change in intercellular communication called
inflammaging which further aggravates the process.
28. CHANGES OF THE BODY IN
AGING
Skeletal changes:
The loss of bone.
•Osteoporosis- defined as a decrease in both mass and strength.
•Osteoarthritis- a degenerative joint disease.
Body build:
2 noticeable changes occur in body build during adulthood
•A decrease in height
•Fluctuations in weight
29. Changes in cardiovascular system:
Age related changes in the heart:
Accumulation of fat.
The stiffening of heart muscle, blood vessels due to tissue changes.
Changes in respiratory system :
With increasing age, the rib cage and the air passageways become
stiffer.
Changes in the maximum amount of air we can take into lungs in a
single breath.
30. Changes of reproductive system
Women:
•The major reproductive change in women is the loss of ability to bear
children
•Begins in the 40s, as menstrual cycles become irregular and by 55
they attain menopause
Men:
•Do not have physiological and cultural event to mark reproductive
changes
•They experience a normative decline in quantity of sperm
31. Changes in endocrine system:
Most apparent in:
•Glucose homeostasis
•Reproductive function
•Calcium metabolism
Subtle in:
•Adrenal function
•Thyroid function
32. Age related skin changes:
•The changes in the skin leads to wrinkling and sagging
•The dermis thins
•Less collagen is produced.
•The elastin fibres that provide elasticity wear out.
•There is decreased function of sebaceous and sweat glands that
contribute to dry skin
• The epidermal cells decreases by 10% per decade and divide more
slowly, as well as become thinner.
33. Observed hair changes:
•There is gradual thinning and graying of hair resulting from cessation
of pigment production of both men and women.
•Hair loss occurs due to destruction of germ centres that produce hair
follicle.
•Men lose the hair about their temples, have receding hairlines or male
pattern baldness.
•Women have receding hairline and thinner hair. There is increased
hair growth around chins and lips.
•Especially near menopause age, ovary functions slow down and there
are more androgens produced causing hirsutism.
34. Changes of brain:
Ageing causes changes to the brain size, vasculature, and cognition.
The brain shrinks with increasing age and there are changes at all
levels from molecules to morphology. Incidence of stroke, white
matter lesions, and dementia also rise with age, as does level of
memory impairment and there are changes in levels of
neurotransmitters and hormones.
Higher levels of education or occupational attainment may act as a
protective factor. Also protective are a healthy diet, low to moderate
alcohol intake, and regular exercise. Biological ageing is not tied
absolutely to chronological ageing and it may be possible to slow
biological ageing and even reduce the possibility of suffering from
age related diseases such as dementia.
