Transcript Aging theories

Aging theories
R-Sharifan , MD
Mashhad-1393
• Childhood
• Adolescence
• Young
• Middle age
• Adulthood
• Aged
What is Aging?
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The gradual and spontaneous changes that occur in maturation
from infant to young adult due to decreased of accommodation
response to stress.
These changes create a normal physiologic decline seen in middle
and late adulthood.
• Decline in basal function
• Reduction in reserve capacity
What is Aging?
• Otto Bismarck
• Older than 60 (65) years (Chronological age)
• According to WHO : 45-59 Middle
60-74 Young old
75-90 Old
over 90 Oldest old
Senescence
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The process by which a cell looses its ability to divide,
grow, and function. This loss of function ultimately ends in
death.
• A degenerative process, only.
• Has no positive features.
Why do we get old?
Why do we get old?
• Intrinsic cellular mechanism (35% ?)
• Environmental influence (65% ?)
• “The link between genes and lifespan is
unquestioned. The simple observation that some
species live longer than others -- humans longer
than dogs, tortoises longer than mice -- is one
convincing piece of evidence.”
• 50 genes for cellular longevity
Why do we get old?
• Gerontology : study of the social, psychological
and biological aspects of aging.
• Aging theories :
• Biological theories
• Psychosocial theories
Biological theories
• Two main biological theories :
• Programmed theories
• Error theories
• Programmed Theories
Aging has a biological timetable or internal biological clock.
• Error Theories
Aging is a result of internal or external assaults that damage cells
or organs so they can no longer function properly.
Many theories are a combination of programmed and error theories.
Programmed vs. Error Theories
Programmed Theories
• Programmed Senescence Theory
• Endocrine Theory
• Immunology Theory
Error Theories
• Wear and Tear Theory
• Rate-of-Living Theory
• Cross-linking Theory
• Free Radical Theory
• Error CatastropheTheory
• Somatic Mutation Theory
Programmed Senescence Theory
• The result of sequential switching “off” or “on” of specific
genes. Aging when occurred that age-related disorders
were happened.
• Example – “Hayflick’s Limits” (1965)
• Fibroblasts removed from umbilical cord & cultured
• Fibroblasts divide and repeated until ~ 50 divisions
• Will not divide past this point
Programmed Senescence Theory
Telomeric Theory
• This is an extension of the “Hayflick Limit.”
• Telomeres are specialized DNA sequences
at the end of chromosomes.
• They shorten with each cell division.
• When the telomeres become too short, the
cell enters the senescence stage.
• In the normal process of DNA replication,
the end of the chromosome is not copied
exactly, which leaves an unreplicated gap.
Programmed Senescence Theory
Telomeric Theory
• The enzyme, telomerase, fills the gap by attaching
bases to the end of the chromosomes.
• As long as the cells have enough telomerase to do the
job, they keep the telomeres long enough to prevent
any important information from being lost as they go
through each replication.
• With time, telomerase levels decrease.
• With decreasing telomerase levels, the telomeres become
shorter and shorter so cell enter to senescence phase.
Programmed Senescence Theory
Telomeric Theory
Shortened telomeres are found in:
• Atherosclerosis
• Heart disease
• Hepatitis
• Cirrhosis
Programmed Senescence Theory
Telomeric Theory
• 90% of cancer cells have been found to possess telomerase.
• Telomerase prevents the telomere from shortening.
• This allows the cancer cells to reproduce, resulting in tumor growth.
• Research areas
• Measuring telomerase may help detect cancer.
• Stopping telomerase may fight cancer by causing death of cancer cells.
• Telomerase may be used to help with wound healing or the immune
response.
Endocrine theory
• Biological clocks act through hormones to control the speed of
aging.
• Hormones effects growth, metabolism, temperature, inflammation
and stress.
• Insulin/IGF-1 has important role in hormonal control of aging.
• Examples- Menopause
• Decreased level of estrogen & progesterone
• Hot flashes, insomnia
Immunologic Theory
• A programmed decline in the immune system leads to
an increased vulnerability to disease, aging and death.
• In puberty immune system has the most potency
• With advanced age dysregulated immune response
was occured and play role in CVS disorder, alzhiemer
and cancer.
• Example- Decreased T cells (helper cells) in adults
• Increased diseases in older adults
• Increased autoimmune diseases in adults
• Example- decreased Ab efficacy and volume
Error theory
Aging is a result of internal or external assaults that damage
cells or organs so they can no longer function properly.
Wear and Tear Theory
Free Radical Theory
Rate-of-Living Theory
CatastropheTheory
Cross-linking Theory
Somatic Mutation Theory
Wear and tear theory
• Years of damage to cells, tissues and organs
eventually wears them out, killing both them and
the body.
• Weismann in 1882
• Example- Wearing out of the skeletal system such
as in osteoarthritis
• Wear and tear can be viewed as a result of aging
and not the cause of it.
Rate-of-Living Theory
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The greater an organism’s basal metabolic rate, the shorter the
life span.
Free radicals or other metabolic by-products play a role.
Example
Animals with the most rapid metabolisms tend to have the
shortest lifespans, i.e, birds have a shorter lifespan than humans.
Studies examining the relationship between metabolic rates and
longevity have produced inconsistent results, limiting the
usefulness of this theory.
Cross-linking theory
• The accumulation of cross-linked proteins damages cells and
tissue, slowing down bodily processes.
• Lohn Bjorksten in 1942
• Example
Non-enzymatic glycosylation reaction occur when glucose
molecules attach to proteins causing a chain of chemical
reactions resulting in a structural change to the proteins.
• Loss of flexibility of connective tissue
• Microvascular changes in arteries
Free Radical Theory
• During aging, damage produced by free radicals cause cells and organs
to stop functioning.
• Gerschmann in 1954 and then Harmans
• A free radical is a molecule with an unpaired, highly reactive electron.
• One type of very reactive free radical is the oxygen free radical or
reactive oxygen species (ROS) , which may be produced during
mithocondrial breathing metabolism or as a result of environmental
pollution.
Free Radical Theory
Free Radical Theory
Free Radical Theory
The free radical “grabs” a electron from any molecule it its vicinity.
It does this because electrons like to exist in pairs.
When it “grabs” an electron from another molecule, it damages
the other molecule.
Free Radical Theory
• Some of the molecules that may be damaged by free radicals are
fats, proteins, and DNA (both in the nucleus and in mitochondria).
• If membrane fats are attacked, then you get the breakdown of the
cell membrane. If it is a red blood cell membrane, you get
hemolysis.
• If proteins are attacked, you get the breakdown of proteins, which
may result in the loss of biological function and the accumulation
of “catastrophic” compounds.
• If DNA is attacked, you will get a mutation that may cause aging or
cancer.
Free Radical Theory
Free Radical Theory
• Free radicals do not go unchecked. The body has a multi-layed
defense system that reacts and detoxifies the damaging radicals.
• Defenses include:
• Natural antioxidants in the body, such as bilirubin.
• Enzymes such as superoxide dismutase (SOD) , catalase, & glutathione
peroxidase.
• Dietary antioxidants such as beta carotene, and the vitamins C and E.
Free Radical Theory
Free Radical Theory
• Under normal conditions, body natural defense mechanisms
prevent most of the oxidative damage from occurring.
• The free radical theory of aging proposes that, little-bylittle, small amounts of damage accumulate and
contribute to deterioration of tissues and organs.
anti-oxidant
molecule
repaired
membrane
damaged
DNA
The anti-oxidant molecule destroys the damaging free radical. The membrane repairs itself,
but the DNA remains damaged, impairing the cells function. In addition, the anti-oxidant
molecule now has an unpaired electron and thus becomes a new radical.
Free Radical Theory
• For example, when Vitamin E “scavenges” free radicals, it becomes a free radical and may
be more carcinogenic than the original free radical.
• This is the reason why taking high doses of vitamin E SUPPLEMENTS appears to INCREASE
cancer risk in a person, not decrease cancer risk.
• Not all free radicals cause damage.
• You use free radicals as part of your immunological response system.
• Macrophages engulf bacteria
• Free radical reactions produced inside the macrophage oxidize and kill bacteria.
Question: Does it make any biological sense to try to eliminate all free radicals in your
body by taking supplements?
Catastophic theory
• Any damage to the enzyme systems that synthesize proteins in
the body results in faulty protein synthesis.
• The faulty proteins continue to accumulate in the cell until they
reach a level that damages the cells, tissues, and organ
• When enough damage accumulates, this may result in cell
malfunctioning ( aging) leading to death.
Somatic mutation theory
• Genetic mutations occur and accumulate with age in the somatic
cell causing the cell to:
• Deteriorate
• Malfunction
• 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.
Psychological Theories of
Aging
Psychological Theories of Aging
1. Full-Life Development Theories (Erik
Erikson)
2. Mature-Life Theories
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2.
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4.
Robert Peck’s Theory
The Activity Theory (Neugarten’s Theory)
The General Theory of Disengagemen
Continuty theory
Full-Life Development Theory
Eric Erickson was one of the first
psychological theorists to develop
a personality theory that extends
to old age.
Full-Life Development Theory
Full-Life Development Theory
Disengagement Theory
• Developed by Cummings and Henry in late 1950’s.
• “aging is an inevitable, mutual withdrawal or
disengagement, resulting in decreased interaction between
the aging person and others in the social system he/she
belongs to.”
• Withdrawall and introspection mechanism.
Activity Theory
• Developed by Robert Havighurst in the 1960’s.
• Supports the maintenance of regular activities, roles, and social
pursuits.
• Persons who achieve optimal age are those who stay active.
• As roles change, the individual finds substitute activities for
these roles.
Continuity Theory
• By Neugarten and co-workers in reaction to the
disengagement theory
• “basic personality, attitudes, and behaviors remain
constant throughout the life span”