Basic pemahaman Telomer pada proses aging dan tumor ganas

1. PERANAN TELOMER PADA PROSES
PENUAAN DAN KEGANASAN AKIBAT
DISTRES
INDAH YULIANTO.D.
ILMU KESEHATAN KULIT DAN KELAMIN
FK UNS / RSUD.Dr.MOEWARDI
SURAKARTA
30/03/2013
Sunday, April 7, 13

2. PERANAN TELOMER PADA PROSES
PENUAAN DAN KEGANASAN AKIBAT
DISTRES
INDAH YULIANTO.D.
ILMU KESEHATAN KULIT DAN KELAMIN
FK UNS / RSUD.Dr.MOEWARDI
SURAKARTA
30/03/2013
Sunday, April 7, 13

3. Proses penuaan
ž Fenomena biologik dengan perubahan yang
terpaut waktu menjurus keproses degeneratif
dan berakhir dengan kematian yang
mekanismenya berlangsung dalam interaksi
biologik, psikologik dan sosial
INDAH YULIANTO – MARET 2013
30/03/2013
Sunday, April 7, 13

4. Proses penuaan
ž Fenomena biologik dengan perubahan yang
terpaut waktu menjurus keproses degeneratif
dan berakhir dengan kematian yang
mekanismenya berlangsung dalam interaksi
biologik, psikologik dan sosial
INDAH YULIANTO – MARET 2013
30/03/2013
Sunday, April 7, 13

5. EVOLUSI HIDUP UMAT CIPTAAN “SANG PENCIPTA”
INDAH YULIANTO – MARET 2013
30/03/2013
Sunday, April 7, 13

6. EVOLUSI HIDUP UMAT CIPTAAN “SANG PENCIPTA”
INDAH YULIANTO – MARET 2013
30/03/2013
Sunday, April 7, 13

7. MENGAPA TELOMER ?
PERANAN TELOMER PADA PROSES
PENUAAN DAN KEGANASAN AKIBAT
DISTRES
INDAH HIDAJATI YULIANTO.D.
ž 1. Telomer merupakan pengulangan urutan DNA yang
ž BAGIAN/SMF.ILMU KESEHATAN KULIT
melindungi kedua ujung kromosom manusia.
2. Pengulangan mencapai UNS/ sampai ribuan kali dari
DAN KELAMIN – FK ratusan
RSUD.DR.MOEWARDI SURAKARTA
nekleotida TTAGGG
3. Pada manusia ada 46 kromosom, jadi ada 92 pasangan
telomer
INDAH YULIANTO – MARET 2013
30/03/2013
Sunday, April 7, 13

8. MENGAPA TELOMER ?
PERANAN TELOMER PADA PROSES
PENUAAN DAN KEGANASAN AKIBAT
DISTRES
INDAH HIDAJATI YULIANTO.D.
ž 1. Telomer merupakan pengulangan urutan DNA yang
ž BAGIAN/SMF.ILMU KESEHATAN KULIT
melindungi kedua ujung kromosom manusia.
2. Pengulangan mencapai UNS/ sampai ribuan kali dari
DAN KELAMIN – FK ratusan
RSUD.DR.MOEWARDI SURAKARTA
nekleotida TTAGGG
3. Pada manusia ada 46 kromosom, jadi ada 92 pasangan
telomer
INDAH YULIANTO – MARET 2013
30/03/2013
Sunday, April 7, 13

9. 30/03/2013
Sunday, April 7, 13

10. Biru : DNA dan Putih : protein telomer
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11. Fungsi telomer dan telomerase
ž Melindungi kedua ujung kromosom dari alur
perbaikan DNA, setiap ada repair diikuti oleh fusi dari
kromosom
ž Telomer mempertahankan panjang kromosom
ž Telomer juga mempunyai kaitan dengan membran
nukleus, berfungsi mem maintain struktur nukleus.
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12. Telomerase
ž Merupakan suatu ribonukleotase enzim kompleks protein (a
cellular reverse transcriptase)
v TERT – RNA : directed DNA polimerase
v TRC : RNA template
ž Mensitesis telomere untuk menjaga kestabilannya dengan
menambah hexameric TTAGGG, berulang pada ujung
kromosom, mengganti telomer yang erosi pada saat proliferasi
sel.
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13. Telomerase terdiri dari dua komponen :
protein dan RNA
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14. Peranan telomer pada proses penuaan
ž Mempunyai kemampuan bersifat imortal (germ cell,
cancer cell), dan dirawat oleh enzim telomerase
ž Sel yang mempunyai kemampuan membelah terbatas
Ø Tidak mempunyai aktivitas telomerase
Ø Terjadi pemendekan telomer yang progresif
Ø Pembelahan sel sebagai “mitotic clock” untuk
replikasi sebagai sel senescence (jompo)
Mekanisme ini dapat dijelaskan pada “Hayflick limit”
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15. Berbagai macam stress yang berperan pada proses
penuaan
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16. Hayflick limit: cells are only
capable of a limited number
of population doublings in
culture.
Here’s what is meant by the
term doubling in vitro.
One serial passage or
Term is used to describe doubling of cells
replication going on in
culture dishes.
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Sunday, April 7, 13

17. Population doublings
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18. The triggers of senescence have been categorized as short telomeres
and as stress although, in the case of the latter, the exact source of the
stress has not been defined. The main pathways responsible for the
establishment of senescence are indicated.
30/03/2013
Sunday, April 7, 13

19. The triggers of senescence have been categorized as short telomeres
and as stress although, in the case of the latter, the exact source of the
stress has not been defined. The main pathways responsible for the
establishment of senescence are indicated.
30/03/2013
Sunday, April 7, 13

20. ž Pada manusia, telomerase aktif pada germ cells,
in vitro immortalized cells, pada sel kanker
and, kemungkinan juga pada beberapa sel
punca.
ž Terlomerase dengan kadar tinggi pada germ
cells, sel punca, sel epidermis, folikel
rambut,dan sel kanker.
ž Dan tidak aktif: sel somatik, sel yang
berdiferensiasi dan paska mitosis.
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Sunday, April 7, 13

21. Sel senescence (jompo)
ž Setelah telomer menyusut sampai batas tertentu,
sel akan berhenti membelah diri, (-) 4 kB pada
manusia merupakan stresor yang mengakibatkan
sel berhenti berproliferasi
ž Akan berakibat perubahan pada aktivitas sel,
dimana sel masuk pada tahap senescence
ž Bentuk sel berubah , ekspresi gen juga berubah
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Sunday, April 7, 13

22. Telomere also provide a means for "counting"
cell division: telomeres shorten with each cycle
Telomeres shorten from 10-15 kb
20 (germ line) to 3-5 kb after 50-60 doublings
(average lengths of TRFs)
Telomere Length (humans)
Cellular senescence is triggered when
cells acquire one or a few
Normal critically short telomeres.
Somatic
10 Cells
(Telomerase
Negative)
Cellular (replicative) Senescence
Number of Doublings
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23. 30/03/2013
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24. (A). Sel fibroblasts yang mengalami
senescence dan (B) Sel fibroblast yang aktif
proliferasi
A
B
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25. Telomere also provide a means for "counting"
cell division: telomeres shorten with each
cycle
Telomeres shorten from 10-15 kb
20 (germ line) to 3-5 kb after 50-60 doublings
(average lengths of TRFs)
Telomere Length (humans)
Cellular senescence is triggered when
cells acquire one or a few
Normal critically short telomeres.
Somatic
10 Cells
(Telomerase
Negative)
Cellular (replicative) Senescence
Number of Doublings
30/03/2013
Sunday, April 7, 13

26. Telomere also provide a means for "counting"
cell division: telomeres shorten with each
cycle
Telomeres shorten from 10-15 kb
20 (germ line) to 3-5 kb after 50-60 doublings
(average lengths of TRFs)
Telomere Length (humans)
Cellular senescence is triggered when
cells acquire one or a few
Normal critically short telomeres.
Somatic
10 Cells
(Telomerase
Negative)
Cellular (replicative) Senescence
Number of Doublings
30/03/2013
Sunday, April 7, 13

27. The triggers of senescence have been categorized as short telomeres
and as stress although, in the case of the latter, the exact source of the
stress has not been defined. The main pathways responsible for the
establishment of senescence are indicated.
30/03/2013
Sunday, April 7, 13

28. The triggers of senescence have been categorized as short telomeres
and as stress although, in the case of the latter, the exact source of the
stress has not been defined. The main pathways responsible for the
establishment of senescence are indicated.
30/03/2013
Sunday, April 7, 13

29. Kanker
ž Ada berbagai macam jenis kanker yang dapat
mengenai tubuh manusia
ž Yang menjadi dasar dari sel kanker adalah
pertumbuhan yang tidak terkontrol serta sel yang
bersifat imortal
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30. Kanker (lanjutan)
ž Kanker muncul ketika sel mengalami mutasi
genetik dibarengi oleh kejadian sel melepaskan
diri dari kontrol normal pada replikasi dan migrasi
ž Sel dan keturunannya berkembang biak tak terkendali,
dapat menyerang dan merusak jaringan di dekatnya.
Melalui metastasis, sel-sel dapat menyerang darah
terdekat atau pembuluh limfatik, mengakibatkan
keganasan baru di tempat yang jauh.
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31. Telomerase and Cancer
ž In theory, a lack of telomerase would retard the growth of
tumors by causing continually dividing cells to lose their
telomeres and to die before they did any damage.
ž Therefore, the removal of telomerase could be a possible
treatment for cancer.
ž In regard to this theory, many experiments have been
conducted to detect telomerase in cancers versus normal
somatic tissue.
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32. Telomerase and Cancer - Study
ž The treated cells continued to divide long after they would
normally enter senescence.
ž In most of the cells, the telomeres shortened drastically
and the cells eventually died. However, some cells
persisted and became immortal.
ž In these immortal cells, the telomeres were maintained at a
significantly short length.
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Sunday, April 7, 13

33. Telomerase and Cancer -
Study
ž The treated cells continued to divide long after they would
normally enter senescence.
ž In most of the cells, the telomeres shortened drastically
and the cells eventually died. However, some cells
persisted and became immortal.
ž In these immortal cells, the telomeres were maintained at a
significantly short length.
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38. Future Trends
ž Telomerase has many diagnostic, therapeutic and
prognostic potential applications for the future.
ž One of the potential applications of telomerase is to
postpone cellular aging by delaying critical telomere
loss therapeutically, through reactivation of
telomerase.
ž If the telomerase is reactivated in cells that have
gone into senescence, the cells could continue to
divide and bypass cellular aging.
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39. TERIMAKASIH ATAS
PERHATIANNYA
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40. TERIMAKASIH ATAS
PERHATIANNYA
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