Theory of aging

1. Theories of Aging
Under supervision:Dr naglaa ghida
Presented : Nourhan Dahshan

2. Contents
1. Definition
2. Historical Perspective
3. Theories of Aging
 Developmental Genetic
Theories
 Stochastic Theory
4. Conclusion

3. Definition
AGING:
Denham Harman postulates that aging is the result
of progressive accumulation of changes in the
body which occur with passing time and which
cause the increase in the probability of the disease
and death of the individual.

4. WHY DO WE AGE?
•IS IT GENETICS?
•ENVIRONMENTAL
DAMAGE?

5. HISTORICAL ASPECTS
• Research on aging began around twentieth century.
• Metchnikoff introduced concept that aging was
caused by continuous absorption of toxins from
intestinal bacteria, and received noble prize in 1908.
• Systematic studies that described the aging
phenomena in terms of all morphology, physiology
and biochemistry began about 1950.

6. • There was an improvement in experimental
designs that led to accurate definition of valid
and reliable hypotheses.
• Current modified versions of aging theories
have been introduced that involve the
immune system, the neuroendocrine system,
failures in DNA repair, mutation of cells, errors
in proteins and damage from free radicals

7. Two major aging theories have evolved from
those studies.
1. DEVELOPMENTAL GENETIC THEORY
2. STOCHASTIC THEORY

8. THE BIG QUESTION
DEVELOPMENTAL—
GENETIC THEORIES
• Genetic makeup
determines factors
directly affecting
aging
• Programmed &
directed in the body
• Aging is
Predetermined
ENVIRONMENTAL NON-
GENETIC THEORIES
•Due to random events
that occur over time
•Aging caused by
environmental damage
•Controlled extrinsically

9. Theories of Aging
1. STOCHASTIC THEORIES/ NON-GENETIC
THEORY
These theories states that aging is caused by an
accumulation of insults from the environment
Results of these insults is that the organisms eventually
reaches a level incompatible with life

10. Stochastic Theories
• Cross-linkage theory
• Error theory
• Redundant DNA theory
• Somatic mutation theory

11. CROSS-LINKAGE
THEORY/GLYCOSYLATION THEORY
• 1942, Johan Bjorksten first related the concept of
cross-linkage to developmental aging
• It is binding of glucose to protein that causes various
problems
• Cross-linking hypothesis is based on the observation
that with age our proteins, DNA and other structural
molecule develop inappropriate attachments or cross
link to one another.

12. Proposed Chemical
reaction of Cross Linking of
Macromolecules related to
aging
Occurred during sun
tanning--lose elasticity
Loss of Tissue
Elasticity
These unnecessary links or
bonds decrease the
mobility or elasticity of
proteins and other
molecules.

13. • Cross-linking of skin proteins collagen, e.g.
wrinkles and other age related dermal damage.
• Bjorksten implies that cross linking is primary
cause of sclerosis, failure of immune system and
loss of elasticity.
• Loss of flexibility of the aging body is due to
cross linking of tendons, ligaments and muscle
tissue

14. Error theory/ error catastrophe theory
• Orgel in 1963.
• DNA--RNA--protein synthesis
• Basis:
1)errors can occur in the transcription in any step
of the protein synthesis of DNA
2) error causes the reproduction of an enzyme or
protein that is not an exact copy
3) As transcription errors to occur, the end
product would not even resemble the original
cell, thereby compromising its functional ability

15. Error CRISIS
• If the error containing protein molecule is one that
is involved in synthesis of genetic material or in
the protein synthesizing machinery however then
the molecules could cause further errors resulting
in error crisis.
• “Error Crisis” result in impaired cell function

16. Limitations of Error theory
• Theory was discarded due to lack of experimental
supporting evidence although altered proteins due occur
in aging mammals.
• More recently the theory has not been supported
by research
– not all aged cells contain altered or misspecified proteins
– nor is aging automatically or necessarily accelerated if
misspecified proteins or enzymes are introduced into a
cell
Error theory is no longer regarded as viable theory.

17. REDUNDANT DNA THEORY
• Medvedev suggested that biological changes in
aging are a result of accumulating errors in
functioning genes.
• Accumulation of these takes over the system
until it is exhausted.
• Medvedev writes that different species life span
may be a function of the degree of repeated
genetic sequences.

18. Limitations:
• It failed to explain other possible aging
factors, such as radiation induced aging
and quantative aspects of normal
aging.

19. SOMATIC MUTATION THEORY
• This theory emerged following the world war 2 as
a result of increased research in the area of
radiation biology
• Theory hypothesis that mutations/genetic
damage results from radiation and radiomimetic
agents accumulate and eventually create
functional failure and ultimately death to
organisms

20. • Accumulation of mutations result in :
–Damage to the DNA
The theory states that aging is an
imbalance between DNA’s ability to
repair itself and accumulating DNA damage.
–When the damage exceeds the repair, the
cell malfunctions and this can lead to
senesence.

21. Limitations:
• Life span shortening by radiation doesn’t
define whether or not the life span
mechanism bears any relationship to the
normal mechanism of aging

22. 2] Developmental-genetic theories
• This theory consider the process of aging to be
part of a continuum with development
genetically controlled and programmed.
• Supporting evidence for the genetic basis of
aging and maximal life span comes from the
recognition of genetic diseases of precocious
aging, such as in genetic progeroid syndromes

23. Developmental Genetic theories
• Free radical theory
• Calorie restriction theory
• Hayflick limit theory
• Neuroendocrine and hormonal theory
• Immunological theory

24. 1] Free radical theory
• What are radicals and how are they formed ?
• Free radical is any atom/molecule that has a single unpaired electron
in an outer shell therefore they are unstable and highly reactive.
• This theory was proposed by Dr.Denham Harman
• He stated that free radical derived from oxygen are responsible for
damage associated with aging.

25. • Free radicals have been shown to damage cell
membrane, lysosome, mitochondria and nuclear
membranes through a chemical reaction called
Lipid-peroxidation.
• Free radicals are rapidly destroyed by protective
enzymes.
• Some free radicals escape destruction and cause
damage to important structures eventually
interfering with their functions and causing death.

26. • Alcohol, tobacco, heavy metals, pesticides and other
chemicals, some medications, radiation, diet, and
strenuous exercise all accelerate the production of
free radicals.
• Consuming excess calories generates excess free
radicals. This may explain why calorie restriction has
been shown to increase life-span as fewer free
radicals are produced.
• In nervous and muscle tissue to which free radicals
have high affinity a substance called lipofuscin has
been found and is thought to be indicative of
chronological age.

27. • Lipofuscin (lipid $ protein-
enriched pigmented material) has
been found in older population
commonly referred as “AGE
SPOTS”.
• As lipofuscin increases ,healthy
tissue is deprived of oxygen.
• This theory was highly accepted
because it provides mechanism of
aging and doesn’t depends on
tissue specific action but its
fundamental at all aerobic tissues.

28. Metabolism, Free Radicals, & Life Span
• Accumulates Over Time from
Oxygen Metabolism
• Free radicals associated with
atherosclerosis, cancer
• Metabolic Rate Directly Related
to Free Radical Production
• Inverse Relationship Between
Metabolic Rate & Life Span
• Hypothesis--Lower metabolic
rate, lower free radical
production, increase life span

29. 2] Calorie Restriction Theory
• This theory is defined as reduction in calorie ,
intake while maintaining essential nutrients
requirements.
• Dr. Walford had committed himself to
high/low diet with moderate vitamins and
minerals supplementation and a regular
exercise regimen.
• Gradually lose weight until maximal metabolic
efficiency, retards aging

30. • Experimental mammalian models of caloric
restriction reduce caloric intake by 40%
throughout lifespan of animal.
• This proved to be beneficial at a various level
of functions and involving a number of
molecules, cellular and systematic changes.
• Caloric restricted diet influences both aging
rate and disease susceptibility.

31. Limitations:
• Some studies revealed that calorie restriction
affects immunity and slow the DNA repair
capacity

32. 3] HAYFLICK LIMIT THEORY
• One of the first proposed biologic theory is based on a
study completed in 1961 by Hayflick and Moorehead.
• Landmark Study--Cells Have Time-clock
• Cells Have Limited Life Span
– Apoptosis=Programmed cell death
– They showed that there are functional changes that
do occur within cells and are responsible for aging of
cells and organisms.

33. • Based on lab experiments on fetal fibroblastic
cells and their reproductive capabilities in
1961.
• Cells can only reproduce themselves a limited
number of times.
• Life expectancies are seen as preprogrammed
within a species-specific range.

34. Developmental process of cells has 3
phases:
Phase
1
•Beginning stage of life
Phase
2
• Cell proliferation
Phase
3
• Cessation of cell division

35. • Hayflick showed that phase 3 is nearly
between 40 and 60 population doubling for
embryo cells .
• He stated nutrition has an effect on cells with
overfed cells dividing is much faster than
underfed cells.
• Evidence of Hayflick limit has also seen in
cultures taken from individually with progeria.

36. 4] NEUROENDOCRINE AND HORMONAL
THEORY
• This theory regards functional
decrements in neurons and
their associated hormones as
central to the aging process.
• Aging Mediated in Brain
• Functional Decrements in
neurons and associated
hormones dictates aging rates
• He based his theories on past
studies of hypothyroidism a
disease that mimics mature
aging.

37. • He proposed that the hypothalamic, pituitary and
adrenal axis is the master timekeeper for the
organisms and primary regulator of aging process.
• Best explained with following examples:
1. With increasing age there is decline in growth
hormone secretion that results in decrease in
insulin like growth factor production in liver and
other tissues.
2. Decrease in gonadotropin releasing hormone from
hypothalamic neurons results in decline of
luteinizing hormone which is the primary factor in
loss of reproduction cycles in female

38. Limitations:
• Critics of the theories, however point out that
the master timekeeper of aging lacks
universality i.e. many organisms that age have
no complex neuroendocrine system .

39. 5] Immunological Theory
• It is categorized as a developmental genetic
theory proposed by Walford.
• It explains that the rate of aging is controlled
by the immune system and as we age it
declines.

40. • It is based on two major observations:
1. There's decrease is functional capacity of immune
system with decline in age as a result reduced
resistance to infectious disease.
2. Fidelity of immune system is declined with age as
evidenced by striking age-associated increase in
autoimmune diseases.

41. Limitations:
• Its difficult to defend the immune system’s
role as the primary time keeper in biology of
all organisms.

42. Maslow's Hierarchy of Needs

43. • Erikson’s theory breaks down psychosocial
development into eight stages.
• These stages are delineated by age and
characterized by a struggle or crisis that must
be overcome in order to adapt and continue
to develop
• Each stage consists of healthy and unhealthy
Erik Erikson

44. ERIKSN’S STAGES of personaity and ego
development

45. CONCLUSION
• Two major categories of theories exist
1. Genetic based theory
2. Non genetic theory
But question remain the same why do we age?
What causes aging?
No single theory explains entire process of
growing old

46. ‘THANK YOU’