2. 1.The Free Radical Theory
( by Denham Harman in 1956 )
• A free radical describes any molecule that has a free electron, and this
property makes it react with healthy molecules in a destructive way.
• Because the free radical molecule has an extra electron it creates an
extra negative charge. This unbalanced energy makes the free radical
bind itself to another balanced molecule as it tries to steal electrons.
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3. Cont;
• In so doing, the balanced molecule becomes unbalanced and thus a
free radical itself. Perhaps a bit like bumper-cars crashing into each
other at the Fair?
• It is known that diet, lifestyle, drugs (e.g. tobacco and alcohol) and
radiation etc., are all accelerators of free radical production within the
body.
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4. Cont;
• Free radicals are known to attack the structure of cell membranes,
which then create metabolic waste products.
• Such toxic accumulations interfere with cell communication, disturb
DNA, RNA and protein synthesis, lower energy levels and generally
impede vital chemical processes.
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5. Cont;
• Free radicals can however be transformed by free-radical scavengers (anti-
oxidants). Particular anti-oxidants will bind to particular free radicals and
help to stabilize them.
• Free radicals come in a hierarchy according to their potential for damage.
• A cross-section of anti-oxidants is important in order for the process of
elimination of the free radicals to occur, and it is even possible to convert
higher damage free radicals into lower damage free radicals.
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6. Cont;
• Such a broad cross-section of anti-oxidants includes substances such
as beta carotene, vitamin C, grape seed extract, vitamin E , Hydergine,
Melatonin and Vinpocetine.
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7. Cont;
• It is therefore necessary to take a cross-section of anti-oxidants in order
for the process of elimination of the free radicals to occur, otherwise higher
damage free radicals may be converted into a greater number of lower
damage free radicals. Free radicals damage the DNA.
• The Free radical theory is also referred to as the Oxidative Damage theory
of aging.
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8. 2. The Neuroendocrine Theory of Aging
• Was first proposed by First proposed by Professor Vladimir Dilman
and Ward Dean MD.
• It stresses on wear and tear by focusing on the neuroendocrine
system, that govern the release of hormones under the instructions
of the hypothalamus.
• The hypothalamus controls various chain-reactions to instruct other
organs and glands to release their hormones.
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9. Cont;
• But as we grow older the hypothalamus loses it precision regulatory
ability and the receptors which do the uptake of individual hormones
become less sensitive to them.
• Subsequently , as people age the secretion of many hormones
declines and their effectiveness is also reduced due to the receptors
down-grading.
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10. Cont;
• It is theorized that the hypothalamus loss of regulation it is damaged
by the hormone cortisol.
• Cortisol is produced from the adrenal glands and is responsible for
stress. Cortisol is one of the few hormones that increases with age.
• Hence; more age, more cortisol production, more hypothalamic
damage, more loss of hormonal regulatory capacity, more aging.
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11. 3.Cross-Linking Theory
• The Cross-Linking Theory of Aging is also referred to as the
Glycosylation Theory of Aging.
• In this theory it is the binding of glucose to protein, (a process that
occurs under the presence of oxygen) that causes various problems.
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12. Cont;
• Once this binding has occurred the protein becomes impaired and is
unable to perform efficiently.
• Hence the longer the life this leads to the increased possibility of
oxygen meeting glucose and protein
• Examples of cross-linking disorders include senile cataract and the
appearance of tough, leathery and yellow skin.
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13. Cont;
• Research shows that individuals with diabetes have 2-3 times the
numbers of cross-linked proteins when compared to their healthy
counterparts.
• The cross-linking of proteins may also be responsible for cardiac
enlargement and the hardening of collagen, which may then lead to
the increased susceptibility of a cardiac arrest.
• Cross linked proteins have also been implicated in renal disorders.
• It is also theorized that sugars binding to DNA may cause damage that
leads to malformed cells and thus cancer.
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14. Cont;
• The modern diet is of course a very sweet one and we are bombarded
with simple sugars from soft drinks and processed foods etc.
• Therefor one obvious example to reduce the risk of cross-linking is to
reduce sugar and also simple carbohydrates in ones diet.
• Some pharmacological interventions that could help reduce the
carbohydrate/ starch/ glucose intake and affect, include The modern
diet is of course a very sweet one and we are bombarded with simple
sugars from soft drinks and processed foods etc.
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15. Cont;
• One obvious example to reduce the risk of cross-linking is to reduce
sugar (and also simple carbohydrates) in the diet.
• Some pharmacological interventions that could help reduce the
carbohydrate/ starch/ glucose intake and affect, include Acarbose and
Metformin.
• Supplements such as Aminoguanidine and the amino-acid Carnosine
have also shown great influence in the battle to prevent, slow and
even break existing cross-links.
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16. 4.THE GENOME MAINTENANCE THEORY OF AGING
Damage to our DNA happens thousands of times every day in every cell
in our body throughout our lives.
This damage can be caused by oxidative free radicals, mistakes in
replication, or outside environmental factors such as radiation or
toxins.
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17. Cont;
Mutations or spontaneous changes in the structure of our genes that
occur in our egg or sperm cells will be passed on to future generations,
if those mutations are not so potentially disruptive as to be fatal to our
offspring.
Mutations that occur in the rest of the cells of the body will only affect
that individual and cannot be passed on to future generations.
Most of those body cell, or somatic, mutations will be corrected and
eliminated.
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18. Cont;
• They will then accumulate, eventually causing the cells to malfunction
and die.
• This process, it has been suggested, is a crucial component in the
aging process.
• This theory also encompasses a role for mitochondria, the cellular
powerhouses, as important factors in aging.
• Mitochondria create damaging free radicals as a by-product of normal
energy production.
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19. Cont;
• Somatic mutations in the DNA of the mitochondria accumulate with
age, increasing free radical production, and are associated with an
age-related decline in the functioning of mitochondria.
• Many scientists believe that mitochondrial aging is an important
contributor to aging in general.
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20. Cont;
• Our bodies have repair mechanisms to take care of much of that
damage.
• Defects in DNA repair seem to be directly related to aging.
• Evidence exists for the decline in DNA repair and the accumulation of
DNA damage in several different types of cells taken from elderly
subjects.
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21. Cont;
• Elderly patients’ blood and skin cells have less capacity to repair
themselves than those from young adults.
• In a study that looked into white blood cells found DNA damage in
two to four percent of the cells from young adults, but six times more
often in cells from the elderly.
• These aging white blood cells with their higher level of DNA damage
may explain some of the decline in immune function associated with
aging.
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22. Cont;
• Additionally, scientists have linked Werner’s syndrome, a rare disease
of premature aging, to mutations in the WRN gene.
• These mutations lead to abnormalities in DNA replication and repair
of DNA damage.
• Poor capacity for DNA repair is also linked to the most prevalent
disease of aging ; cancer.
• Exploring the role of DNA damage and repair remains a critical area
of aging research.
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26. 5.Evolutionally Theories of Aging
The major evolutionary theories of aging constitute the;
i) Programmed death theory of aging ( by August Weismann)
ii) Mutation accumulation theory of aging (by Peter Medawar)
iii) the antagonistic pleiotropy theory of aging (by George Williams).
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27. i). The Mutation Accumulation theory
• Considers aging as a by-product of natural selection.
• The probability of an individual reproducing depends on his age.
• It is zero at birth and reaches a peak in young adults, after which it
decreases due to the increased probability of death linked to various
external and internal (senescence) factors.
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28. Cont;
• In such conditions, deleterious mutations expressed at a young age
are severely selected against, due to their high negative impact on
fitness (number of offspring produced).
• On the other hand, deleterious mutations expressed only later in life
are rather neutral to selection, because their bearers have already
transmitted their genes to the next generation.
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29. Cont;
• In this theory, persons loaded with a deleterious mutation have fewer
chances to reproduce if the deleterious effect of this mutation is
expressed earlier in life.
• For example, patients with juvenile progeria live only for about twelve
years and therefore, they cannot pass their mutant genes to the next
generation.
• In such conditions, the progeria stems only from new mutations and
not from the genes of parents.
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30. Cont;
• People expressing a mutation at older ages can reproduce before the
illness occurs, as it is the case with familial Alzheimer's disease.
• As an outcome, progeria is less frequent than late diseases, such as
Alzheimer's disease, because the mutant genes responsible for the
Alzheimer's disease are not removed from the gene pool as readily as
progeria genes, and can thus accumulate in successive generations.
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31. Cont;
• According to the mutation accumulation theory, one would expect
the genetic variability for life span (in particular, the additive genetic
variance responsible for familial resemblance) to increase with age.
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32. ii). Antagonistic Pleiotropy Theory Of Aging
The theory is based on two assumptions;
First, it is assumed that a particular gene may have an effect not only
on one trait, but on several traits of an organism (pleiotropy).
The second assumption is that these pleiotropic effects may affect
individual fitness in opposite (antagonistic) ways.
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33. Cont;
• The theory suggests the existence of so-called pleiotropic genes (those
demonstrating favorable effects on fitness at a young age and deleterious
ones at old age), which could explain the aging process.
• Such genes are maintained in the population due to their positive effect on
reproduction at a young age, despite their negative effects at a post-
reproductive age (their negative effects in later life will look exactly like the
aging process).
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34. Cont;
• For illustration, suppose that there is a gene that increases the
fixation of calcium in bones.
• Such a gene may have positive effects at a young age, because the
risk of bone fracture and subsequent death is decreased, but negative
effects in later life, because of increased risk of osteoarthritis due to
excessive calcification.
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35. Cont;
• Antagonistic pleiotropy theory explains why reproduction may come
with a cost for species longevity, and may even induce death
• Any mutations favoring more intensive reproduction (more offspring
produced) will be propagated in future generations even if these
mutations have some deleterious effects in later life.
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36. Cont;
• For example, mutations causing overproduction of sex hormones may
increase the reproductive efforts, and reproductive success— and
therefore be favored by selection, despite causing prostate cancer (in
males) and ovarian cancer (in females) later in the life.
• Therefore, the idea of reproductive cost, or, more generally, of trade-
offs between different traits follows directly from antagonistic
pleiotropy theory.
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37. iii). Programmed theory of Aging
• August Weismann (1834 - 1914) was a noted German evolutionary
biologist considered by some to be the most important 19th century
evolutionary thinker after Darwin.
• In 1882 he published a theory of mammal aging to the effect that
programmed death accomplished an evolutionary purpose and that
therefore animals were designed to have a limited life span.
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38. Cont;
• Darwin had earlier proposed that the evolution process was
extremely incremental and proceeded in "tiny steps." If this was so,
younger animals in any evolving population would tend to be
minutely more evolved (adapted) than older animals.
• Weismann's idea was that programmed death assisted the evolution
process by removing older animals from the population and thus
freeing resources (food supply, habitat) for younger organisms
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39. Cont;
• However, Weismann did not have effective arguments against the
objections and eventually recanted.
• Weismann's theory was subsequently largely ignored or taught as a
scientific venture.
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40. Cont;
• However, in the late 20th century there was a renewed interest in
programmed aging.
• First, There is now substantial agreement that aging (as opposed to
death, per se) does have evolutionary consequences.
• Aging causes weakness, increased susceptibility to disease and
environmental conditions, reduced mobility, and reduced sensory
acuity, all of which plausibly reduce survival and reproduction
potential.
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