Post on 15-Apr-2017
“The link between genes and lifespan is
unquestioned. The simple observation that
some species live longer than others-
humans live longer than dogs, tortoises
longer than mice- is one convincing piece of
evidence”- The National Institute of Aging-
Compiled by: Ayu Yussof
WHAT IS AGING?
Everyone intuitively knows what ‘aging’ means, but it is quite difficult to give the exact
definition of aging. These are some of the widely accepted definitions of aging:
Aging is inevitable physiological changes occurring in organisms over time. It
ultimately ‘leads to death naturally as one gets old along with gradual dysfunctions of
all organs in the organisms’. Aging is the direct cause of diseases and death in humans.
Along with growth, aging proceeds once human are born. Based upon aging, many
physiological phenomena such as reduction in the number of cellular tissues, a
decrease of the metabolic rate, an increase of diseases and loss of adaptability take
place. The progression of aging is a degenerative change associated with biological
characteristics rather than being determined by environmental factors and ultimately
indicates that the probability of death is rapidly increasing. The environmental factors
that are relevant to lifestyle including stress, exercise, smoking and exposure to
sunlight either accelerate the progression of aging.
The processes that occur during life which culminate in changes that decreased an
individual’s ability to handle biological challenges.
The gradual and spontaneous changes that occur in maturation from infant to young
adult. These changes create a normal physiologic decline seen in middle and late
adulthood.
Aging is initiated based on genetic and environmental factors that operate from the
time of birth of organisms. Aging induced several physiological phenomena such as
reduction of cell counts, deterioration of tissues proteins, tissue atrophy, a decrease of
the metabolic rate, reduction of body fluids and calcium metabolism abnormalities.
This phenomena leads to several vital impairments such as cardiopulmonary,
neurological, endocrine function, as well as motor function impairments. Therefore,
the exposure to risk factors including hypertension, smoking, hyperlipidemia, glucose
metabolism impairment, obesity, food, lifestyle, alcohol and stress induced multiple
diseases in various body system e.g.
- Nervous central system: Along with aging, the number of cerebral nerve cells is
reduced by approximately 20% in cerebral blood flow. The size of the brain is
then reduced slightly and some neurons are lost in selected part of the brain such
as locus ceruleus, subsantia nigra, hippocampus, caudate nucleus, putamen and
cerebral cortex. However, there are no sufficient studies showing that the
functions of the brain are markedly impaired due to aging.
Dementia, degenerative diseases, stroke, cataract and hearing loss.
- Neuroendocrine system: It has been well known that the loss of some neurons is
accompanied in the neuroendocrine system by aging.
hormone imbalance
- Cardiopulmonary system: hypertension, arteriosclerosis, heart failure,
arrhythmias and pulmonary emphysema.
- Digestive system: Stomach ulcer and diverticulum.
- Metabolic system: Diabetes
Compiled by: Ayu Yussof
- Renal system: Kidney failure
- Skeletal system: Osteoporosis and degenerative arthritis
THEORIES OF AGING
“The link between genes and lifespan is unquestioned. The simple observation that some
species live longer than others- humans live longer than dogs, tortoises longer than mice-
is one convincing piece of evidence”- The National Institute of Aging-
All aging begins with genetics
Aging changes the biochemical and physiological processes in the body
Cell and molecular biologists examine and propose theories to explain the aging
process
- What causes aging?
- How can you manipulate aging, thus prolong life?
THE MAIN CATEGORIES IN THEORY OF AGING.
1. Programmed theories: Aging has a biological timetable or internal biological clock
- The programmed theories imply that aging follows a biological timetable,
perhaps a continuation of the one that regulates childhood growth and
development. This regulation would depend on changes in gene expression
that affect the system responsible for maintenance, repair and defense
responses.
2. Error theories
- Aging is the result of internal or external assault that damage cells or organs
so they can no longer function properly.
- The error theories emphasize environmental assaults to living organisms that
induce cumulative damage at various levels as the cause of aging.
PROGRAMMED VS. ERROR THEORIES
PROGRAMMED THEORIES ERROR THEORIES
1. Programmed senescence theory
2. Endocrine theory
3. Immunology Theory
Wear and tear theory
Rate-of-living theory
Cross-linking theory
Free radical theory
Error Catastrophe theory
Somatic mutation theory
Hayflick’s Cellular Clock Theory
Compiled by: Ayu Yussof
PROGRAMMED THEORIES
1. PROGRAMMED SENESCENCE THEORY
Senescence can be defined as a process by which organisms proceed through a
physical deterioration of the body. It is a complex biological process in which changes
at molecular, cellular and organ levels result in an escalating, inexorable and
ineluctable decrease of the body’s ability to respond appropriately to internal and/or
external stressors (Chodzko-Zajko & Ringel, 1987). Senescence is a degenerative
process by which a cell loses its ability to divide, grow and function. This loss of
function ultimately ends in death.
Example:
i. Telomeric Theory:
- Telomerase are specialized DNA sequences at the end of chromosome.
**They shorten with each cell division.
**When the telomeres become too short, the cell enters the senescence stages.
- In the normal process of DNA replication, the end of the chromosome is not
copied exactly, which leaves an unreplicated gap.
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.
Compiled by: Ayu Yussof
2. ENDOCRINE THEORY
Biological clocks act through hormones to control the pace of aging. Hormones
effects growth, metabolism, temperature, inflammation and stress.
Examples: Menopause
- Decreased level of estrogen and progesterone
- Hot flushes, insomnia
3. IMMUNOLOGIC THEORY
A programmed declined in the immune system leads to an increased vulnerability to
disease, aging and death.
Examples: Decreased T cells (helper cells) in adults
- Increased diseases in older adults
- Increased autoimmune diseases in adults
ERROR THEORIES
1. WEAR AND TEAR THEORY
Years of damage to cells, tissues and organs eventually wear them out, killing both
them and the body.
Example: Wearing out the skeletal system such as osteoarthritis
Wear and tear can be viewed as a result of aging and not the cause of it.
2. RATE-OF-LIVING THEORY (Pearl, 1928)
“Human possessed a finite amount of some vital substance. When that substance is
consumed, we die.”
The greater an organism’s basal metabolic rate, the shorter the life span.
Free radicals or other metabolic by-product play a role in senescence.
Example: Animal with the most rapid metabolism tend to have the shortest lifespan,
i.e, birds have a shorter lifespan than human.
Studies examining the relationship between metabolic rates and longevity have
produces inconsistent results, limiting the usefulness of this theory.
3. CROSS-LINKING THEORY (Dr. Johan Bjorksten, 1968)
The accumulation of cross-linked proteins damages cells and tissue, slowing down
bodily processes.
Example: Non-enzymatic glycosylation reactions 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
Compiled by: Ayu Yussof
4. FREE RADICAL THEORY (Dr. Denham Harman, 1954)
Free radical is a term used to describe any molecule that differs from conventional
molecules which possessed a free electron, a property that makes it react with other
molecules I highly volatile and destructive ways.
In a conventional molecule, the electrical charge is balanced. Electrons come in pairs
so that their electrical energies cancel each other out. Atoms that are missing electrons
combine with atoms that have extra electrons, creating a stable molecule with evenly
paired electrons and a neutral electrical charge.
The free radical, on the other hand, has an extra negative charge. This unbalanced
electrical energy tends to make the free radical attach itself to other molecules as it
tries to steal a matching electron to attain electrical equilibrium. By doing so, they
created more free radicals and extensive bodily damage.
Free radicals attack the structure of our cell membranes, creating metabolic waste
products, including substances known as lipofuscins (aging spots). These lipofuscins
in turn interfere with the cells’ ability to repair and reproduce themselves. They
disturb DNA & RNA synthesis, interfere with synthesis of protein, deplete energy
level
The free radical "grabs" electron from any molecule in 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.
Compiled by: Ayu Yussof
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 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.
However, free radicals do not go unchecked. The body has multi-layers of defense
system that reacts and detoxifies the damaging radicals. The 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 vitamins C and E.
Under normal conditions, the body natural defense mechanisms prevent most of the
oxidative damage from occurring. The free radical theory of aging proposes that, little
by little, small amounts of damage accumulation contribute to the deterioration of
tissues and organs.
5. HAYFLICK LIMIT: CELLULAR CLOCK THEORY
Dr. Leonard Hayflick & Dr Paul Moorhead discovered that human cells have a
limited capacity to reproduce themselves in culture of dividing. This limitation is
believed to be determined by the length of cell’s telomeres. It was believed by
scientists that telomere shortening is the answer to human aging process. However, in
human not all types of tissue contain actively replicating cells. Example, brain cells
and muscle cell of the heart does not have replicating activity. The scientists conclude
that while telomeres may contribute to aging but does not govern it.
Compiled by: Ayu Yussof
1. MOLECULAR THEORIES
Codon restriction – Accuracy of mRNA translation is impaired due to inability to
decode codon in mRNA.
Error catastrophe (Dr. Leslie Orgel, 1963)
- Fidelity of gene expression decline with age, resulting in increased fraction of
abnormal proteins.
- 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 (Dr. Leo Szilard, 1959)
- Accumulation of molecular damage, primarily to DNA / genetic material.
- Genetic mutation 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 repair, the cell malfunctions and this can lead to
senescence.
Dysdifferentiation – Gradual accumulation of random molecular damage impairs
regulation of gene expression.
Gene regulation – Aging caused by changes in gene expression regulating both
aging & development.
Biological Theories Of Aging
Molecular theories
Cellular theories
System theories
Evolutionary theories
Compiled by: Ayu Yussof
2. CELLULAR THEORIES
Wear & tear – Accumulation of normal injury.
Free radical – Oxidative metabolism produces highly reactive free radicals that
subsequently damage proteins and DNA (B. Ames, 10 and R. Melhom, 12)
Apoptosis – programmed cell death resulting from genetically determined events
or genomes crisis (J. Campisi, 11)
Senescence – Phenotypes of aging are caused by an increased in frequency of
senescent cells. Senescence may be the result from telomere loss (replicative
senescence) or cell stress (cellular senescence)
3. SYSTEM THEORIES
Rate of living – Assumes a fixed amount of metabolic potential for every living
organisms (live fast, die young)
Neuroendocrine (Prof. Vladimir Dilman of Petrov Institute of Oncology, St.
Petersberg, Russia, 1983) – Alteration in neuroendocrine control of homeostasis
results in age-related physiological changes. (P.S Timiras, F. Yaghmaie, 35)
Immunologic – Well documented decline of immune function with age results in
increased incidence of disease. (H. Stemberg, 25+26)
4. EVOLUTIONARY THEORIES
Disposable soma – somatic cells are maintained only to ensure continued
reproductive success; following reproduction the soma is disposable.
Life span theory – Different organisms vary dramatically in their lifespan.
Obviously aging negatively affects the duration of life since it increases the risk of
death. These intrinsic, maladaptive effects of aging, unchecked by selection, are,
however, not the only factors affecting the length of life. Independent of whether
aging occurs or not, reproductive lifespan can evolve adaptively in response to
selection for increased reproductive success (Stearns 1992)
Mutation accumulation – Mutations that affect health at older ages are not selected.
According to Medawar ‘s MA hypothesis (1946, 1952); if the effects of a
deleterious mutation were restricted to late ages, when reproduction has largely
stopped and future survival is unlikely, carriers of the negative mutation would
have already passed it on to the next generation before the negative late-life
Compiled by: Ayu Yussof
effects would become apparent. In such situation, natural selection would be weak
and ineffective at eliminating such mutation and over evolutionary time such
effectively neutral mutation would accumulate in the population by genetic drift,
which in turn would lead to the evolution of aging.
Antagonistic pleiotropy – Genes that are beneficial at younger ages are deleterious
at older ages. George C. Williams (1957) argued Medawar’s MA hypotheses; if it
is true that selection cannot counteract deleterious effects at old age, he argued,
then mutations or alleles might exist that have opposite, pleiotropic effects at
different ages: genetic variants that are on one hand exhibit beneficial effects on
fitness early in life, when selection is strong, but on the other hand have
deleterious effects late in life, when selection is already weak. This hypotheses is
known today as the AP hypothesis for the evolution of aging (Rose 1991, Flatt &
Promislow 2007, Figure 3B)
ERIC ERIKSON’S THEORY: FULL LIFE DEVELOPMENT THEORY
The 1st psychological theorist to develop a personality theory that extends to old
age.
Erikson’s approach in perspective is influential and comprehensive; it covers
entire life span. He believed that not everyone passes through stages at the same
time.
Psychological Theories Of
Aging
Full-life development theories
(Erikson's Theory)
Mature-life theory
1. Robert Peck's
2. Neugarten's Theory
Compiled by: Ayu Yussof
STAGE PSYCHOSOCIAL CRISIS BASIC VIRTUE AGE
1 Trust vs Mistrust Hope 0 - 1 ½
2 Autonomy vs Shame Will 1 ½ - 3
3 Initiative vs Guilt Purpose 3 – 5
4 Industry vs Inferiority Competency 5 – 12
5 Ego Identity vs Role Confusion Fidelity 12 – 18
6 Intimacy vs Isolation Love 18 – 40
7 Generativity vs Stagnation Care 40 – 65
8 Ego Integrity vs Despair Wisdom 65+
ROBERT PECK’S: MATURE LIFE THEORY
STAGE 1
EGO DIFFERENTIATION
VS
WORK-ROLE PERFORMANCE
For those who invested heavily in their
careers, finding other ways to affirm self-
worth through family, friendship, and
community life.
STAGE 2
BODY TRANSCENDENCE
VS
BODY PREOCCUPATION
Surmounting physical limitations by
emphasizing the compensating rewards of
cognitive, emotional and social powers.
STAGE 3
EGO TRANSCENDENCE
VS
EGO PREOCCUPATION
As contemporaries die, facing the reality of
death constructively through efforts to make
life more secure, meaningful, and gratifying
for younger generations.
BERNICE NEUGARTEN’S: MATURE LIFE THEORY
A person must remain as active as possible.
Age-graded expectations for life event
Compiled by: Ayu Yussof
SUMMARY
1. MAIN CATEGORIES IN AGING
2. CLASSIFICATION OF AGING THEORIES
BIOLOGICAL THEORIES OF AGING PSYCHOLOGICAL THEORIES OF AGING
Molecular Theories
Cellular Theories
Evolutionary Theories
System Theories
FULL DEVELOPMENT THEORIES
- Eric Erikson’s Theories
MATURE-LIFE THEORIES
- Robert Peck’s Theories
- Bernice Neugarten’s Theories
Programmed Theories
• Programmed Senescence Theories
• Endocrine Theories
• Immunology Theories
Error Theories
• Wear & Tear Theories
• Rate-of-Living Theories
• Cross-Linking Theories
• Free Radical Theories
• Error Catastrophe Theories
• Somatic Mutation Theories
• Hayflick's Cellular Clock Theories