KASHMEERA N.A.KASHMEERA N.A.II SEM. M.Sc. ZOOLOGYII SEM. M.Sc. ZOOLOGYROLL No: 37ROLL No: 37CHRIST COLLEGE ,IJKCHRIST COLLEGE ,IJK

Gerontology (from Gerontology (from Greek:  :  gerongeron, "old man" and-, "old man" and-logy, , "study of") is the study of the "study of") is the study of the social, , psychological and  and biological aspect of  aspect of aging..

It is distinguished fromIt is distinguished fromgeriatrics, which is the branch , which is the branch of medicine that studies the of medicine that studies the diseases of the elderly. of the elderly.

Characteristics of aging affect all the individuals of a Characteristics of aging affect all the individuals of a species.species.

Two major topics in research on agingTwo major topics in research on aging

1)1) Life spanLife span

2)2) SenescenceSenescence

These topics are interrelated.These topics are interrelated.

Many evolutionary biologists consider senescence to be the default state Many evolutionary biologists consider senescence to be the default state occuring after the animal has fulfilled the requirements of natural selection.occuring after the animal has fulfilled the requirements of natural selection.

After its offspring are born and raised,the animal can die.eg:Pacific salmonAfter its offspring are born and raised,the animal can die.eg:Pacific salmon

Recent studies indicate that there are genetic components that regulate Recent studies indicate that there are genetic components that regulate rate of aging.Altering activity of these genes can alter lifespan of an rate of aging.Altering activity of these genes can alter lifespan of an individual.individual.

The maximum lifespan is a characteristic of The maximum lifespan is a characteristic of a species;a species;

It is the maximum number of years a It is the maximum number of years a member of species has been known to member of species has been known to survive.survive.

Life expectancy is not a characteristic of Life expectancy is not a characteristic of species,but of populationsspecies,but of populations

It is the age at which half the population still It is the age at which half the population still survives.survives.

Life expectancy of IndiansLife expectancy of Indians

♂ ♂ ♂ ♂ - 65.77 years ; ♀ ♀ - 67.95 years- 65.77 years ; ♀ ♀ - 67.95 years

Nuclear pyknosis: With advancing age, the nucleus shrinks and stains deeply. This is due to the condensation of the nuclear material.

Aging is accelerated by chromosomal aberrations,and somatic gene mutations

Degeneration of cytoplasmic organelles

Changes in enzymatic proteinsChanges in enzymatic proteins

LDH,SDH,AC Pase,Lysosomal enzymes

Catalase,Glutathione peroxidase

Respiratory enzymes,Alkaline phosphatase,Glucose dehydrogenase

telomeres -specific DNA sequences found only at the tips of chromosome.

protect the tips of chromosomes from erosion and from sticking to one another.

in most normal body cells each cycle of cell divisionshortens the telomeres.

Eventually, after many cycles of cell division,the telomeres can be completely gone and even some ofthe functional chromosomal material may be lost.

erosion of DNA from the tips of our chromosomescontributes greatly to aging and death of cells.

Shortening of telomeresShortening of telomeres

Accumulation of aging pigmentsAccumulation of aging pigments

Lipofuscin accumulation

Accumulation of free radicals

Free radicals produce oxidative damage in lipids, proteins, ornucleic acids by “stealing” an electron to accompany theirunpaired electrons.

Some effects are wrinkled skin, stiff joints,and hardened arteries.

Normal metabolism—for example, aerobic cellular respiration in mitochondria—produces some free radicals.

Others are present in air pollution, radiation, and certain foods we eat. Naturally occurring enzymes in peroxisomes and in the cytosol normally dispose of free radicals.

Accumulation of free radicalsAccumulation of free radicals

Ward Dean M.D.

Changes in hormonal levelsChanges in hormonal levels

Weakened immune systemWeakened immune system

With age the system's ability to produce necessary antibodies that fight disease declines

the immune system may start to attack the body’s own cells.

This autoimmune response might be caused by

changes in cell-identity markers at the surface of cells that cause antibodies to attach to and mark the cell for destruction.

Decrease in rate of celldivisionDecrease in rate of celldivision

The Hayflick Limit Theory of Aging says that the human cells ability to divide is limited to approximately 50-times, after which they simply stop dividing (and hence die).

Leonard Hayflick

Glucose, the most abundant sugar in the body, plays a role in the aging process.

It is haphazardly added to proteins inside and outside cells, forming irreversible cross-links between adjacent protein molecules.

With advancing age, more cross-links form,which contributes to the stiffening and loss of elasticity that occur in aging tissues.

The changes occuring in the intercellular spaces and in the lumen of blood The changes occuring in the intercellular spaces and in the lumen of blood vascular system are examples of extracellular changes.vascular system are examples of extracellular changes.

DementiaDementia

Dementia (taken from Latin, originally meaning "madness", from de- "without" + ment, the root of mens "mind") is a serious loss of cognitive ability .

dementia is common in the geriatric population,

Dementia is a non-specific illness syndrome (i.e., set of symptoms) in which affected areas of cognition may be memory, attention, language, and problem solving.

one of the most common forms of dementia is Alzheimer's disease

In Alzheimer’s disease, a substance called amyloid builds up and causes the early death of brain cells, which results in a progressive loss of memory and other brain functions.

Alzheimer’s diseaseAlzheimer’s disease

Atherosclerosis is a disease in which plaque builds up inside arteries.

Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood.

Over time, plaque hardens and narrows arteries.

This limits the flow of oxygen-rich blood to organs and other parts of body.

Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death.

Atherosclerosis Atherosclerosis

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue .

This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue.

Eg: cirrhosis of the liver.

cirrhosis of the liver fibrosis in heart

FibrosisFibrosis

Parkinson's disease is a degenerative disorder of the central nervous system.

The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the region of the midbrain;

the cause of this cell death is unknown.,

the most obvious symptoms are movement-related; these include shaking, rigidity, slowness of movement and difficulty with walking and gait.

dementia commonly occur in the advanced stages of the disease.

Other symptoms include sensory, sleep and emotional problems.

PD is more common in the elderly-after the age of 50.

Parkinson's diseaseParkinson's disease

Changes in collagenChanges in collagen

There is an increase in the amount of collagen proteins There is an increase in the amount of collagen proteins deposition in the intercellular spaces. This influences the deposition in the intercellular spaces. This influences the permeability of cell membranes, affects the speed of diffusion of permeability of cell membranes, affects the speed of diffusion of substances in and out and significantly influences the process of substances in and out and significantly influences the process of aging.aging.

Wrinkles are a by-product of the aging process. Wrinkles are a by-product of the aging process.

With age, skin cells divide more slowly, and the inner layer, called With age, skin cells divide more slowly, and the inner layer, called the dermis, begins to thin. the dermis, begins to thin.

The network of elastin (the protein which causes skin to stretch) The network of elastin (the protein which causes skin to stretch) and collagen fibers (the major structural proteins in the skin), and collagen fibers (the major structural proteins in the skin), which support the outer layer, loosen and unravel, causing which support the outer layer, loosen and unravel, causing depressions on the surface. depressions on the surface.

With aging, skin also loses its elasticity, is less able to retain With aging, skin also loses its elasticity, is less able to retain moisture, oil-secreting glands are less efficient and the skin is moisture, oil-secreting glands are less efficient and the skin is slower to heal. slower to heal.

All of these contribute to the development of wrinklesAll of these contribute to the development of wrinkles

Aging and WrinklesAging and Wrinkles

Oxidative damageOxidative damage

Aging is a by-product of normal metabolism;

About 2- 3% of the oxygen atoms taken up by the mitochondria are reduced to reactive oxygen species (ROS).

[Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen ]

These ROS include the superoxide ion, the hydroxyl radical, and hydrogen peroxide.

ROS can oxidize and damage cell membranes, proteins, and nucleic acids.

Evidence for this theory includes the observation that Drosophila that overexpress enzymes that destroy ROS(catalase and superoxide dismutase) live 30 -40% longer than do controls .

Moreover, flies with mutations in the methuselah gene live 35% longer than wild-type flies.

The methusaleh mutants have enhanced resistance to paraquat, a poison that works by generating ROS within cells

. These findings not only suggest that aging is under genetic control, but also provide evidence for the role of ROS in the aging process.

In C. elegans, too, individuals with mutations that increase the synthesis of ROS-degrading enzymes live much longer than wild-type nematodes .

The evidence for ROS involvement in mammalian aging is not as clear.

Mitochondrial genome damage.Mitochondrial genome damage.

It is thought that mutations in mitochondria could (1) lead to defects in energy production, (2) lead to the production of ROS by faulty electron transport, (3) induce apoptosis.

A recent report shows that there are "hot spots" for age-related mutations in the mitochondrial genome,

and that mitochondria with these mutations have a higher replication frequency than wild-type mitochondria.

Thus, the mutants are able to outcompete the wild-type mitochondria and eventually dominate the cell and its progeny.

Moreover, the mutations may not only allow more ROS to be made, but may make the mitochondrial DNA more susceptible to ROS-mediated damage.

General wear-and-tear and genetic General wear-and-tear and genetic instabilityinstability

"Wear-and-tear" theories of aging are among the oldest hypotheses

.As one gets older, small traumas to the body build up.

Point mutations increase in number, and the efficiencies of theenzymes encoded by our genes decrease.

if a mutation occured in a part of the protein synthetic apparatus, the cell would make a large percentage of faulty proteins .

If mutations arose in the DNA-synthesizing enzymes, the rate ofmutations would be expected to increase markedly, .

Likewise, DNA repair may be important in preventing senescence, and species whose members' cells have more efficient DNA repairenzymes live longer

genetic defects in DNA repair enzymes can produce premature aging syndromes in humans

Progeria is a disease characterized by normal developmentin the first year of life followed by rapid aging.

It is caused by a genetic defect in which telomeres are considerably shorter than normal.

Symptoms include dry and wrinkled skin, total baldness, and birdlike facial features.

Death usually occurs around age 13.

Progeria [Progeria [Hutchinson-Gilford syndromeHutchinson-Gilford syndrome ]

Werner syndrome is a rare, inherited disease that causes a rapid acceleration of aging, usually while the person is only in his or her twenties.

It is characterized by wrinkling of the skin,

graying of the hair and baldness, cataracts,

muscular atrophy, and a tendency to develop diabetes mellitus,

cancer, and cardiovascular disease.

Most afflicted individuals die before age 50.

Werner syndromeWerner syndrome

In C. elegans, there appear to be at least two genetic pathways that affect aging.

The first pathway involves the decision to remain a larva or to continue growth.

After hatching, the C. elegans larva proceeds through four instar stages, after which it can become an adult

or (if the nematodes are overcrowded or if there is insufficient food) can enter a nonfeeding, metabolically dormant dauer stage.

It can remain a dauer larva for up to 6 months, rather than becoming an adult that lives only a few weeks.

In the dauer stage, adult development is suppressed, and extra defenses against ROS are synthesized.

If some of the genes involved in this pathway are mutated, adult development is allowed, but the ROS defenses are still made.

The resulting adults live twice to four times as long as wild-type adults

The pathway that regulates dauer formation & longevity – insulin signalling pathway

Insulin like proteinInsulin like protein

++

DAF2DAF2

TGF –TGF –

Mediated Mediated signalsignal

DAF9DAF9

Steroid Steroid hormonehormone

DAF12DAF12 Gene response for Gene response for reproductive reproductive

growthgrowth

Dauer larva

Proposed mechanism for extending lifespan Proposed mechanism for extending lifespan of C.elegans through insulin signalling of C.elegans through insulin signalling

pathwaypathway

The second pathway involves the gonads.

Germ cells appear to inhibit longevity,

when these cells are removed ,C.elegans live longer.

Germ line stem cells produce a substance that blocks the effects of a longevity- inducing steroid hormone

The insulin signalling pathway also regulates lifespan in Drosophila.

Flies with weak loss-of-function mutations of insulin receptor gene live nearly 85% longer than wild type.

The insulin signalling pathway also regulates lifespan in mammals.

1] mice with loss-of-function mutations of insulin signalling pathway live longer than wild type.

2]dog breeds with low levels of insulin-like growth factor[IGF1] live longer than those breeds with higherlevels of this factor.

3]mice lacking 1 copy of IGF1 receptor gene live 25% longer than wild type.

As human life expectancy increases As human life expectancy increases due to our increased ability to due to our increased ability to

prevent and cureprevent and curedisease, we are still left with a disease, we are still left with a

general aging syndrome that is general aging syndrome that is characteristic of our species.characteristic of our species.

However our knowledge of However our knowledge of regeneration is being put to use by regeneration is being put to use by medicine,and we may soon be able medicine,and we may soon be able

to ameliorate some of the to ameliorate some of the symptoms of agingsymptoms of aging