KULIAH GERIATRI SEMESTER V FK UNUD 2006

AGING PROCESS

Maria Esther Heredia de Capovilla ,116 y.o Ekuador (Guinness Book Dec 2005)

Dr.RA.Tuty Kuswardhani Suastika, SpPD, KGer

* GERIATRIC INSTALATION SANGLAH HOSPITAL * GERIATRIC DIVISION INTERNAL MEDICINE DEPARTEMENT MEDICAL FACULTY UDAYANA UNIVERSITY

BIOLOGIC AGING

The importance of genetics in the regulation of biologic aging is demonstrated by the characteristic longevity of each animal species. Several theories of aging have been promulgated and recently reviewed (Goldstein, 1989; Abrass, 1991). These theories fall into two general categories: accumulation of damaged to informational molecules, or the regulation of specific genes

Why do we Age?

WE DO NOT SEE THE WORLD AS IT IS, WE SEE THE WORLD AS WE CARE

The Tolmud

AGING : IS A PROCESS TO RELEASE THE ABILITY OF TISSUE SLOWLY TO REPAIR/TO CHANGE IT SELF & TO KEEP THE STRUCTURE & THE NORMAL FUNCTION SO IT CAN NOT STAND TOWARD INJURY & TO DEVELOP THE DAMAGE.

(Constantine,1994)

Progressively the human will loose the defence of infection & it will accumulate more metabolic and structural dystortion which is called : DEGENERATIVE DISEASE

AGING PROCESS THEORY

1. GENETIC CLOCK THEORY

In this theory aging has been programmed genetically for certain species. Every species has nucleus like a genetic clock which has been winded according to a certain replication. This clock will count the mytocys Mytocys will stop

The cell replication if it is not winded

This concept is supported by the reality that the explanation : Why on some species get a real different of life expectation
Figure 1. Record in life span (Eudililin et al, 1993)
Turtle 170 y.o

Elephant
Horse Gorilla

70 y.o
62 y.o 48 y.o

Bear
Cat Dog

47 y.o
30 y.o 27 y.o

Theoritically it is possible to rewind this clock eventhough just for small time, with same external interverences, such as : Health development Disease prevention with medicine/ treatment
The theory supported by experiment : nucleus which determines the replication Aging Death

2. THE DAMAGE OF IMMUNE SYSTEM

The repeated mutation/ the changing protein post translation decrease the immune system ability to recognized it self The somatic mutation antigen disorder in the cell to cause immune system treat the changing cell as a strange cell and destroy it. Auto immune process antigen antibody reaction in different tissues aging effect histo incontability reaction in multi tissue auto antibody prevalency All somatic cell will set aging process, except sexual cell & cell which is getting mutation to be a cancer.

IMMUNE SYSTEM Is all mechanism used by the body to keep the unity of the body as the prevention against the danger caused by the material in the environment
IMMUNE RESPON Interaction of some immune system component of the body in human

natural immune system

(Non specific)

Immune system

specific immune system

NON SPECIFIC IMMUNE SYSTEM

Body defence against the attack of different microorganism non specific caused it is not led to specific microorganism

THE COMPONENTS OF NON SPECIFIC IMMUNE SYSTEM 1. MECHANISM PHYSIC DEFENCE

Skin Mucus membran Cillia breathing

2. BIOCHEMISTRY DEFENCE Secret of nucans secretion Sebaceus gland skin 3. HUMORAL DEFENCE It contains of complement, interferon, CRP

Specific immune system different ability from non specific immune system in recognizing a strange cell. The first strange cell appears in the body is soon recognized by specific immune system. It stimulate the sensctation of the cell in the immune system. If again the immune system cell is facing the same strain cell it will be more easily to recognized it to destroy

Specific immune system Humoral specific immune system The roler : lymphocyte B (cell B) comes from multipoten cell B cell stimulated by strange Cell proliferate & differensiate plasma cell antibody substation serum The function of antibody : to prevent the body against the bacterial (infection,virus and can do toxin neutralizing)

cellular specific immune system The roler is lymphocyte T (T cell) T cell from multipoten cell but it proliferate & differentiate in the thymus gland It is different from B cell, T cell contain of several subset cell which has different function. The main function of T cell is to help B cell in producing antibody, recognizing & destroying the virus infected cell, activate macrophag in phagocytosis, and controlling limit and the quality of immune system. T cell contain of T helper (Th), T supresor (Ts), T cytotoxix (Tc)

In the elderly in immune system is thymus gland atrophy changing humoral & cellular immune. Aging process causes the immune senescene infection, cancer, autoimmune disease.

Specific Immune The changing of specific immune : I. CELLULAR IMMUNITY a. Thymus gland Thymus hormone stimulates diferensiation, expression & function of lympocyte T because involution gland occurs in the early life T lymphocyte cell diferensiation is decreasing during the aging process. Thymus involution causes immune system dysfunction

T lymphocyte cell proliferation disorder

In the elderly the T lymphocyte cell proliferation responseis decreasing no percentage cell In the blood enzym phosporilation

II. HUMORAL IMMUNITY The lost of the body ability to prevent the antigen a. Volume of B lymphocyte cell volume of B cell apoptotis b. Function of B lymphocyte cell specific antibody production. c. Immunoglobulin In the elderly the increasing of IgG and IgA IgM and IgD IgE constant except atopic patient IgE

3. METABOLIC AGING THEORY From the experiment it get a longer life span caused by the retriction of the calorie. It is caused by one of metabolism process the decrease of hormone excretion will stimulate cell proliferation, such as insulin The modification of under exercise to be more active will cause the longer life span

Mechanism of Caloric Restriction The degree of Caloric Restriction needed to achieve an anti aging effect is far too severe to be a practical preventive regimen for more than a tiny fraction of the human population. to define the biochemical mechanism by which Caloric Restriction alters age dependent physiologic decline is likely to provide the best clues to clinically useful preventive strategies. One line of inquiry starts with the set of known, dramatic changes induced by the Caloric Restriction protocol & attempts to see whether any of these can by itself accomplish some or all of the Caloric Restriction effect.

4. FREE RADICAL THEORY

The free radical are : super oxide (O2), Hydroxcyl radical (COH), Hydrogen peroxide (H2 O2). Free radical is destroyer it is very reactive it can react to DNA *The body itself is able to prevent free radical with its enzymes : superoxide dismutase (SOD) : Zn, Cu, Mn it change superoxide 2O2

2 O2- + 2H+

SOD

H2 O2 + O2

*Catalase enzyme with Fe element in the haem to burst hydrogen peroxide become water & oxygen :
CATALASE

2H2 O2

2H2O + O2

*Glutathion peroxide enzyme with selenium (Se) element burst peroxide hydrogen through the reaction :

H2O2 + GSH

GSSH +H2O

5. WEAR-AND-TEAR THEORY

Supports the concept that aging is a programmed process. each animal-each cell, has a specific amount of metabolic energy available to it & that the rate at whish this energy is used determines the animals length of life. In addition to the depletion of available energy,wearand-tear theories include the effects of the accumulation of harmful by products of metabolism & of faulty enzymes due to random errors as contributing to aging changes

Table Major theories on aging

Theory Accumulation of damaged to informational molecules Mechanisms Spontaneous mutagenesis Failure in DNA repair systems Errors in DNA, RNA, and protein synthesis Superoxide radicals and loss of scavenging enzymes Appearance of specific protein(s) Manifestations Copying errors

Error catastrophe Oxidative cellular damage Genetically programmed senescene

Regulation of specific genes

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