AGING

Penuaan
Walaupun kita mempunyai kemampuan pemahaman
tentang proses penyakit dan juga terapi, kita tetap
akan mati.
Seperti juga spesies yang lain kita juga punya batas
umur (life span)
Proses penuaan didasari faktor endogen (genetic)
serta faktor eksogen, yang pada akhirnya akan
menentukan umur harapan hidup (life expectancy)
Definisi
Penuaan bisa dianggap sebagai akumulasi acak dari kerusakan pada
sel yang menyusun tubuh
 Aging Process

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 Aging Process
Cellular senescent is multifactorial
involves the commutative effects of
both:
Intrinsic molecular clock of cellular aging telomer
Extrinsic stressors of the cellular environment (wear
& tear theory)

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 Proses
Penuaan

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 Intrinsic Cellular Aging
Human fibroblasts in culture have finite
life span:
Adult human fibroblast in culture stop dividing and
become senescent after about 50 doublings
Hayflick phenomenon
Fibroblast from neonates go through about 65
doublings before they cease dividing
Progeria patient: only 35 doublings

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 Aktivitas Telomerase

Short, multiply repeated

sequenc of nontranscribed
DNA (TTAGGG)

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Aging-associated disease
is a disease that is most often seen with increasing frequency with
increasing senescence.
Essentially, aging-associated diseases are complications arising from
senescence.
Age-associated diseases are to be distinguished from the aging
process itself because all adult animals age, save for a few rare
exceptions, but not all adult animals experience all age-associated
diseases.
Peran Heat-shock Protein dalam proses aging

Jenis protein yang normal ada dalam sel dapat

menahan jejas yang dapat menimbulkan
cedera
Ada 2 keluarga: Hsp70 & Hsp60
Jejas yang meningkatkan ekspresi Hsp:
- jejas iskemik : kardial & neuronal
- jejas reperfusi : jantung kelinci
- jejas toksik : adriamisin

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Heat-shock protein
A great deal of research has focused on changes to the
proteolytic machinery in the ageing cell, in particular the
proteasome
Although failure of heat shock proteins (HSPs) to bind
and deliver oxidised proteins efficiently to the degrada-
tion machinery could also contribute to their aggregation
and accumulation.
Oxidised proteins can be protease-resistant and may
even directly inhibit the proteolytic machinery of the cell
Heat-shock protein
The critical role that is played by HSPs in preventing accumulation of
oxidised proteins is often overlooked.
The key role played by HSPs in recognising, removing and preventing
the formation of oxidised and damaged proteins in cells.
The evidence supporting the view that failure of one of these
pathways could underlie ageing and age-related diseases.
Modulation of HSP-activity could influence the ageing process and the
progression of age-related diseases.
 Progeria

A 10-year old girl shows the

typical features of premature
aging associated with progeria

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Aging-associated disease
Aging-associated diseases do not refer to age-specific
diseases, such as the childhood diseases chicken pox
and measles.
"Aging-associated disease" is used here to mean
"diseases of the elderly".
Nor should aging-associated diseases be confused
with accelerated aging diseases, all of which are
genetic disorders.
 Hutchinson-Gilford Progeria Syndrome. HGPS is a childhood disorder caused by mutations in one of the
major architectural proteins of the cell nucleus. In HGPS patients the cell nucleus has dramatically
aberrant morphology (bottom, right) rather than the uniform shape typically found in healthy
individuals (top, right).
Examples of aging-associated diseases are
atherosclerosis and cardiovascular disease,
cancer,
arthritis,
cataracts,
osteoporosis,
type 2 diabetes,
hypertension and Alzheimer's disease.
The incidence of all of these diseases increases rapidly with aging
(increases exponentially with age, in the case of cancer).
 Comparison of a normal aged brain (left) and the brain of a person with Alzheimer's disease (right). Characteristics
that separate the two are pointed out
Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence linking the gene or its product to human longevity
and/or multiple age-related phenotypes
Description
A transcription factor of the Fox family, FOXO3 is crucial in development [802].
It also appears to regulate apoptotic signals in conjunction with FAS and AKT1.
A homologue of FOXO3, daf-16, has been associated with ageing in roundworms [
628], and overexpression of another homologue, dFOXO, in adult fat body of fruit
flies increased longevity in females [1238].
Female mice without FOXO3 showed an ovarian phenotype of follicular activation
leading to oocyte death, early depletion of functional ovarian follicles, and
secondary infertility [625].
Two studies of genetic variation within FOXO3A, have found it to be associated with
exceptional longevity, among people of japanese [1987] and german [1983] origin.
Protein interactions and network
Apoptosis
Kematian / hilangnya sel-sel tunggal yang tersebar di antara sel
sehat,
merupakan suatu bentuk kematian yang telah didisain untuk
mengeliminasi sel-sel yang
tidak dikehendaki,
melalui seri aktivitas peristiwa oleh satu set produk gena yang
bertanggungjawab,
yang terkoordinasi dan terprogram secara internal

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 Peran apoptosis
1. Dalam masa tumbuh kembang
2. Mekanisma homeostatik untuk
memelihara populasi sel dalam jaringan
3. Mekanisma pertahanan pada reaksi imun
4. Pada saat sel diserang penyakit atau
bahan berbahaya
5. Pada proses penuaan

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 Apoptosis in Physiologic Stuations
The programmed destruction of cells during embryogenesis
Hormone dependent involution in the adults endometrial cells
breakdown during menstrual cycle, ovarian follicular atresia in menopause,
regressing lactating breast after weaning, prostatic atrophy after castration
Cell deletion in proliferating cell populations intestinal crypt
epithelia, in order to maintain constant number
Death of host cells that have served their useful purpose
neutrophils in an acute inflammatory response, and lymphocytes at the
end of an immune response
Elimination of potentially harmful self-reactive lymphocytes
before or after completed maturation
Cell death induced by cytotoxic T cells defense mechanism against
viruses and tumors, and cellular rejection of transplan

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 Apoptosis in Pathologic Condition

Cell death produced by a variety of injurious stimuli

radiation therapy and chemotherapy
Cell injury in certain viral diseases viral hepatitis,
loss of infected cells is largely because of apoptosis
Pathologic atrophy in parenchymal organs after duct
obstruction pancreas, parotid gland, kidney
Cell death in tumors most frequently during
regression

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