KULIAH GERIATRI SEMESTER V KULIAH GERIATRI SEMESTER V

FK UNUD 2006 FK UNUD 2006

AGING PROCESS
AGING PROCESS
Dr.RA.Tuty Kuswardhani Suastika, SpPD, KGer Dr.RA.Tuty Kuswardhani Suastika, SpPD, KGer
* GERIATRIC INSTALATIN SANGLA! !SPITAL * GERIATRIC INSTALATIN SANGLA! !SPITAL
* GERIATRIC DI"ISIN INTERNAL #EDICINE DEPARTE#ENT * GERIATRIC DI"ISIN INTERNAL #EDICINE DEPARTE#ENT
#EDICAL $AC%LT& %DA&ANA %NI"ERSIT& #EDICAL $AC%LT& %DA&ANA %NI"ERSIT&
#aria Esther !eredia de Cap'(i))a ,**+ y.'
Ekuad'r ,Guinness -''k . De/0 12234

-ILGIC AGING
-ILGIC AGING

The importance of genetics in the regulation of

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

$hy do we !ge%
$hy do we !ge%
&
&
$' () *)T S'' T+' $),-( !S .T .S,
$' () *)T S'' T+' $),-( !S .T .S,
$' S'' T+' $),-( !S $' /!,'0
$' S'' T+' $),-( !S $' /!,'0
The Tolmud
The Tolmud

!G.*G #
!G.*G #
.S ! 1,)/'SS T) ,'-'!S' T+' !2.-.T3 )4
.S ! 1,)/'SS T) ,'-'!S' T+' !2.-.T3 )4
T.SS5' S-)$-3 T) ,'1!.,6T) /+!*G' .T
T.SS5' S-)$-3 T) ,'1!.,6T) /+!*G' .T
S'-4 7 T) 8''1 T+' ST,5/T5,' 7 T+'
S'-4 7 T) 8''1 T+' ST,5/T5,' 7 T+'
*),9!- 45*/T.)* S) .T /!* *)T ST!*(
*),9!- 45*/T.)* S) .T /!* *)T ST!*(
T)$!,( .*:5,3 7 T) (';'-)1 T+'
T)$!,( .*:5,3 7 T) (';'-)1 T+'
(!9!G'.
(!9!G'.
(/onstantine,199<"
(/onstantine,199<"

1rogressively the human

1rogressively the human
will loose the defence of
will loose the defence of
infection 7 it will
infection 7 it will
accumulate more
accumulate more
metabolic and structural
metabolic and structural
dystortion which is
dystortion which is
called #
called #
&
&
('G'*',!T.;'
('G'*',!T.;'
(.S'!S'0
(.S'!S'0

AGING PROCESS THEORY
AGING PROCESS THEORY
*. GENETIC CLCK T!ER&
*. GENETIC CLCK T!ER&

.n this theory .n this theory aging has been programmed genetically for aging has been programmed genetically for
certain species. certain species.

'very species has nucleus li=e a genetic cloc= which has been 'very species has nucleus li=e a genetic cloc= which has been
winded according to a certain replication. winded according to a certain replication.

This cloc= will count the mytocys This cloc= will count the mytocys
9ytocys 9ytocys will stop will stop
The cell replication if it is not winded The cell replication if it is not winded

This concept is supported by the reality that

This concept is supported by the reality that
the e>planation # $hy on some species get a
the e>planation # $hy on some species get a
real different of life e>pectation
real different of life e>pectation
4igure 1. ,ecord in life span ('udililin et al, 199?"
4igure 1. ,ecord in life span ('udililin et al, 199?"
Turtle Turtle 1@A y.o 1@A y.o
'lephant 'lephant @A y.o @A y.o
+orse +orse BC y.o BC y.o
Gorilla Gorilla <8 y.o <8 y.o
2ear 2ear <@ y.o <@ y.o
/at /at ?A y.o ?A y.o
(og (og C@ y.o C@ y.o

Theoritically
Theoritically

it is possible to rewind this

it is possible to rewind this
cloc= eventhough Dust for small time, with
cloc= eventhough Dust for small time, with
same e>ternal interverences, such as #
same e>ternal interverences, such as #

+ealth development
+ealth development

(isease prevention with medicine6 treatment

(isease prevention with medicine6 treatment
E
The theory supported by e>periment # nucleus
The theory supported by e>periment # nucleus
which determines the replication
which determines the replication

!ging
!ging

(eath
(eath

1. T!E DA#AGE $ I##%NE S&STE#
1. T!E DA#AGE $ I##%NE S&STE#

The repeated mutation6 the changing protein post translation The repeated mutation6 the changing protein post translation
decrease the immune system ability to recogniFed decrease the immune system ability to recogniFed it self it self

The somatic mutation The somatic mutation antigen disorder in the cell antigen disorder in the cell to to
cause immune system cause immune system treat the changing cell as a strange treat the changing cell as a strange
cell and destroy it. cell and destroy it.

!uto immune process !uto immune process antigen antibody reaction in different antigen antibody reaction in different
tissues tissues aging effect aging effect histo incontability reaction in multi histo incontability reaction in multi
tissue tissue auto antibody prevalency auto antibody prevalency

!ll somatic cell will set aging process, e>cept se>ual cell 7 !ll somatic cell will set aging process, e>cept se>ual cell 7
cell which is getting mutation to be a cancer. cell which is getting mutation to be a cancer.

.995*' S3ST'9
.995*' S3ST'9
.s all mechanism used by the body to =eep the
.s all mechanism used by the body to =eep the
unity of the body as the prevention against the
unity of the body as the prevention against the
danger caused by the material in the
danger caused by the material in the
environment
environment

.995*' ,'S1)*
.995*' ,'S1)*
.nteraction of some immune system
.nteraction of some immune system
component of the body in human
component of the body in human

natural immune system natural immune system
(*on specific" (*on specific"
.mmune system
.mmune system
specific immune system specific immune system

*)* S1'/.4./ .995*' S3ST'9 *)* S1'/.4./ .995*' S3ST'9

2ody defence against the attac= of different microorganism 2ody defence against the attac= of different microorganism non non
specific caused it is not led to specific microorganism specific caused it is not led to specific microorganism

T+' /)91)*'*TS )4 *)* S1'/.4./ .995*' S3ST'9 T+' /)91)*'*TS )4 *)* S1'/.4./ .995*' S3ST'9
1. 9'/+!*.S9 1+3S./ ('4'*/' 1. 9'/+!*.S9 1+3S./ ('4'*/'

S=in S=in

9ucus membran 9ucus membran

/illia breathing /illia breathing

C. 2.)/+'9.ST,3 ('4'*/' C. 2.)/+'9.ST,3 ('4'*/'

Secret of nucans secretion Secret of nucans secretion

Sebaceus gland s=in Sebaceus gland s=in

?. +59),!- ('4'*/' ?. +59),!- ('4'*/'

.t contains of complement, interferon, /,1 .t contains of complement, interferon, /,1

Specific immune system

Specific immune system
different ability from non
different ability from non
specific immune system in recogniFing a strange cell.
specific immune system in recogniFing a strange cell.

The first strange cell appears in the body is soon

The first strange cell appears in the body is soon
recogniFed by specific immune system.
recogniFed by specific immune system.

.t stimulate the sensctation of the cell in the immune

.t stimulate the sensctation of the cell in the immune
system.
system.

.f again the immune system cell is facing the same

.f again the immune system cell is facing the same
strain cell
strain cell
it will be more easily to recogniFed it
it will be more easily to recogniFed it

to destroy
to destroy

Specific immune system

Specific immune system

+umoral specific immune system

+umoral specific immune system

The roler # lymphocyte 2 (cell 2"

The roler # lymphocyte 2 (cell 2"
comes from
comes from
multipoten cell
multipoten cell

2 cell
2 cell
stimulated by strange
stimulated by strange

/ell
/ell
proliferate 7 differensiate
proliferate 7 differensiate
plasma cell
plasma cell

antibody substation
antibody substation
serum
serum

The function of antibody # to prevent the body against

The function of antibody # to prevent the body against
the bacterial (infection,virus and can do to>in
the bacterial (infection,virus and can do to>in
neutraliFing"
neutraliFing"

cellular specific immune system

cellular specific immune system

The roler is lymphocyte T (T cell"

The roler is lymphocyte T (T cell"

T cell from multipoten cell but it proliferate 7

T cell from multipoten cell but it proliferate 7
differentiate in the thymus gland
differentiate in the thymus gland

.t is different from 2 cell, T cell contain of several

.t is different from 2 cell, T cell contain of several
subset cell which has different function.
subset cell which has different function.

The main function of T cell is to help 2 cell in

The main function of T cell is to help 2 cell in
producing antibody, recogniFing 7 destroying the
producing antibody, recogniFing 7 destroying the
virus infected cell, activate macrophag in
virus infected cell, activate macrophag in
phagocytosis, and controlling limit and the Guality of
phagocytosis, and controlling limit and the Guality of
immune system.
immune system.

T cell contain of T helper (Th", T supresor (Ts", T

T cell contain of T helper (Th", T supresor (Ts", T
cytoto>i> (Tc"
cytoto>i> (Tc"

.n the elderly
.n the elderly

in immune system is thymus

in immune system is thymus
gland atrophy
gland atrophy

changing humoral 7 cellular

changing humoral 7 cellular
immune.
immune.

!ging process causes the immune senescene

!ging process causes the immune senescene

infection, cancer, autoimmune disease.

infection, cancer, autoimmune disease.

Spe/i5i/ I66une
Spe/i5i/ I66une

The changing of specific immune #

The changing of specific immune #
I. CELL%LAR I##%NIT&
I. CELL%LAR I##%NIT&
a. Thy6us 7)and
a. Thy6us 7)and
Thymus hormone stimulates diferensiation, e>pression
Thymus hormone stimulates diferensiation, e>pression
7 function of lympocyte T
7 function of lympocyte T
because involution
because involution
gland occurs in the early life
gland occurs in the early life
T lymphocyte cell
T lymphocyte cell
diferensiation is decreasing during the aging process.
diferensiation is decreasing during the aging process.
Thymus involution causes immune system dysfunction
Thymus involution causes immune system dysfunction

T )y6ph'/yte /e)) pr')i5erati'n dis'rder
T )y6ph'/yte /e)) pr')i5erati'n dis'rder

.n the elderly the T lymphocyte cell

.n the elderly the T lymphocyte cell
proliferation responseis decreasing
proliferation responseis decreasing

no
no
percentage cell
percentage cell

.n the blood
.n the blood

enFym phosporilation
enFym phosporilation

... +59),!- .995*.T3
... +59),!- .995*.T3

The lost of the body ability to prevent the antigen

The lost of the body ability to prevent the antigen
a. ;olume of 2 lymphocyte cell volume of 2 cell
a. ;olume of 2 lymphocyte cell volume of 2 cell

apoptotis
apoptotis
b. 4unction of 2 lymphocyte cell
b. 4unction of 2 lymphocyte cell
specific antibody
specific antibody
production.
production.
c. .mmunoglobulin
c. .mmunoglobulin

.n the elderly
.n the elderly
the increasing of .gG and .g!
the increasing of .gG and .g!

.g9 and .g(
.g9 and .g(

.g' constant
.g' constant
e>cept atopic patient
e>cept atopic patient
.g'
.g'

8. #ETA-LIC AGING T!ER&
8. #ETA-LIC AGING T!ER&

4rom the e>periment

4rom the e>periment

it get a longer life

it get a longer life
span caused by the retriction of the calorie. .t
span caused by the retriction of the calorie. .t
is caused by one of metabolism process
is caused by one of metabolism process

the
the
decrease of hormone e>cretion will stimulate
decrease of hormone e>cretion will stimulate
cell proliferation, such as insulin
cell proliferation, such as insulin

The modification of under e>ercise to be more

The modification of under e>ercise to be more
active will cause the longer life span
active will cause the longer life span

Mechanis !" Ca#!$ic Res%$ic%i!n
Mechanis !" Ca#!$ic Res%$ic%i!n

The degree of /aloric ,estriction needed to achieve

The degree of /aloric ,estriction needed to achieve
an anti aging effect is far too severe to be a practical
an anti aging effect is far too severe to be a practical
preventive regimen for more than a tiny fraction of
preventive regimen for more than a tiny fraction of
the human population.
the human population.

to define the biochemical mechanism by which

to define the biochemical mechanism by which
/aloric ,estriction alters age dependent physiologic
/aloric ,estriction alters age dependent physiologic
decline is li=ely to provide the best clues to clinically
decline is li=ely to provide the best clues to clinically
useful preventive strategies.
useful preventive strategies.

)ne line of inGuiry starts with the set of =nown,

)ne line of inGuiry starts with the set of =nown,
dramatic changes induced by the /aloric ,estriction
dramatic changes induced by the /aloric ,estriction
protocol 7 attempts to see whether any of these can
protocol 7 attempts to see whether any of these can
by itself accomplish some or all of the /aloric
by itself accomplish some or all of the /aloric
,estriction effect.
,estriction effect.

<. 4,'' ,!(./!- T+'),3
<. 4,'' ,!(./!- T+'),3

The free radical are # super o>ide ()

The free radical are # super o>ide ()
C C
", +ydro>cyl
", +ydro>cyl
radical (/)+", +ydrogen pero>ide (+
radical (/)+", +ydrogen pero>ide (+
C C
)
)
C C
".
".

4ree radical is destroyer

4ree radical is destroyer
it is very reactive
it is very reactive
it
it
can react to (*!
can react to (*!

HThe body itself is able to prevent free radical with its

HThe body itself is able to prevent free radical with its
enFymes # supero>ide dismutase (S)(" # In, /u, 9n
enFymes # supero>ide dismutase (S)(" # In, /u, 9n

it change supero>ide
it change supero>ide
C)
C)
C C
C )
C )
C C
J J

K C+
K C+
K S)( K S)(
+
+
C C
)
)
C C
K )
K )
C C

H/atalase enFyme with 4e element in the &haem0 H/atalase enFyme with 4e element in the &haem0 to burst to burst
hydrogen pero>ide become water 7 o>ygen hydrogen pero>ide become water 7 o>ygen
#
#

/!T!-!S' /!T!-!S'
C+
C+
C C
)
)
C C


C C
+
+
C C
)
)

K )
K )
C C

HGlutathion pero>ide enFyme with selenium (Se" element HGlutathion pero>ide enFyme with selenium (Se" element
burst pero>ide hydrogen through the reaction # burst pero>ide hydrogen through the reaction #
+
+
C C
)
)
C C
K GS+ GSS+ K+
K GS+ GSS+ K+
C C
)
)

3. 9EAR:AND:TEAR T!ER&
3. 9EAR:AND:TEAR T!ER&

Supports the concept that aging is a programmed

Supports the concept that aging is a programmed
process.
process.
each animalJeach cell, has a specific
each animalJeach cell, has a specific
amount of metabolic energy available to it 7 that the
amount of metabolic energy available to it 7 that the
rate at whish this energy is used determines the
rate at whish this energy is used determines the
animalLs length of life.
animalLs length of life.

.n addition to the depletion of available energy,wearJ

.n addition to the depletion of available energy,wearJ
andJtear theories
andJtear theories
include the effects of the
include the effects of the
accumulation of harmful by products of metabolism
accumulation of harmful by products of metabolism
7 of faulty enFymes due to random errors as
7 of faulty enFymes due to random errors as
contributing to aging changes
contributing to aging changes

Ta;)e #a<'r the'ries 'n a7in7
Ta;)e #a<'r the'ries 'n a7in7
Theory Theory 9echanisms 9echanisms 9anifestations 9anifestations
!ccumulation of !ccumulation of

damaged to damaged to
informational informational
molecules molecules
Spontaneous mutagenesis Spontaneous mutagenesis
4ailure in 4ailure in
(*! repair systems (*! repair systems
'rrors in (*!, 'rrors in (*!,
,*!, and protein synthesis ,*!, and protein synthesis
Supero>ide radicals and loss of Supero>ide radicals and loss of
scavenging enFymes scavenging enFymes
/opying errors /opying errors
'rror catastrophe 'rror catastrophe
)>idative cellular )>idative cellular
damage damage
,egulation of ,egulation of
specific genes specific genes
!ppearance of specific !ppearance of specific
protein(s" protein(s"
Genetically Genetically
programmed programmed
senescene senescene

T!ANK &%
T!ANK &%