The Aging Process
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Transcript of The Aging Process
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THE AGING PROCESS
DEPT. OF PHYSIOLOGY MEDICAL SCHOOL
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Aging berhubungan dengan penurunan progresif pada hampir semua fungsi biologi.
EBM: orang inaktif (sedentary lebih cepat tua dibanding orang aktif/atlet
I. PENDAHULUAN
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Usia Harapan Hidup
• Saat ini: 78 years• In 1900 : 47 years• In 2150 : 150 years• Usia harapan hidup dipengaruhi faktor lingkungan dan gaya hidup
Kelompok tua• 65 – 75 : young old• 75 – 85 : middle old• 85 - > : old• 90 - > : very old
• Saat ini: 78 years• In 1900 : 47 years• In 2150 : 150 years• Usia harapan hidup dipengaruhi faktor lingkungan dan gaya hidup
Kelompok tua• 65 – 75 : young old• 75 – 85 : middle old• 85 - > : old• 90 - > : very old
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1.2 Demographic
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II. AGING PROCESS
Aging is a complex interaction of genetic, chemically, physiology and behavior
Aging is a complex interaction of genetic, chemically, physiology and behavior
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2.1 Basic mechanism of aging process
Mekanisme dasar dari penuaan tergantung pada proses ireversibel dan universal pada tingkat seluler dan molekuler dari dua kategori teori: akumulasi random cedera dan program genetik terkontrol
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• First Category : Akumulasi acak kesalahan struktur protein, Mutasi sel somatik, akumulasi produk sisa metabolisme dan kerusakan radikal bebas
• Second Category :Usia genetik maksimum yang menentukan proses penuaan
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Theory AgingTheory Year Proponent
Waste product theory 1923 Carrel and Ebeling
Wear and tear theory 1924 Pearl
Rate of living theory 1928 Pearl
Neuroendocrine theory 1947 Korenchevsky and Jones
Free radical theory 1955 Harman
Collagen theory 1957 Verzar
Metabolic theory 1957 ; 1961 Carlson et al; Johnson et al
Somatic mutation theory 1959 Sziliard
Error-catastrophe theory 1963 ; 1970 Orgel
Cross – linking theory 1968 Bjorksten
Programmed senescence theory 1969 Hayflick
Immunologic theory 1969 Walform
Evolution theory 1977 Kirkwood
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Pada 1950-an Harman: Teori radikal bebas
Dalil bahwa kerusakan makromolekul seluler akibat produksi radikal bebas dalam organisme aerobik merupakan penentu utama dari rentang hidup.
Versi modern: “Teori stres oksidatif "
Penuaan akibat “Reactive oxygen specific” (ROS) yang menyebabkan perubahan fungsional, kondisi patologis dan bahkan kematian.
.
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A schematic summary of proposed mechanisms by which ROS and oxidative stress could contribute to the process of aging
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Relationship between ROS, Inflamation and Aging
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Reactive oxygen species (ROS) can play a role in cell signaling
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2.2 PERUBAHAN FISIOLOGI PADA PENUAAN
• Pada marker mitokondria, terutama DNA mitokondria,
• Factor trankripsi dan mitochondrial encoded protein menurun pada peningkatan usia.
Molecular LevelMolecular Level
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• Perubahan sel:• Atrofi, perubahan fungsi , kehilangan struktur/integritas sel apoptosic
• DNA sensitif untuk cedera • DNA repair menurun
Cellular AgingCellular Aging
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• Perubahan fungsi fisiologis tubuh• Terjadi kekakuan/rigiditas progresif pada
berbagai sistem, misal:- Cardiovascular - Pulmonary - Musculoskeletal - Renal • Atrofi endokrin & immune system
Tissue and Systemic AgingTissue and Systemic Aging
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Penurunan Kebugaran Fisik Karena Pertambahan Usia
5 10 15 20 25 30 35 40 45 50 55 60 65 70
Dayatahan Kekuatan Kelenturan Kecepatan Intelektual
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• Inflamasi adiposa dan endotel kapiler: metabolic syndrome of aging
• Muscular atrophy : Sarcopenia• Perubahan komposisi tubuh
- Weight Gain - Widening of pelvis- Osteoporosis and osteoarthritis- Increase body fat- Total body water decreases- Type II diabetes- Heart disease
Gejala yang muncul:
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WHY EXERCISE ? VO2-Max (A) Cardiac Output (A) Resting Heart-Rate (A) Blood Pressure (A) Body Fat (A,W,K) Metabolism Rate (A,O) Muscle Mass (O) Capillary Density (A) Mitochondrial Density (A) HDL (A) Muscle Strength (W)
Counteract Osteoporosis (W)Counteract Obesity (A,O) Improved Efficiency of the
Muscle (A) Improved Vascularization
(A) Risk of Disease & Stroke
(A) Improved Blood Sugar
Control (A) Improved Structure &
Function of Ligaments & Joints (W,K)
Self Esteem (A,W,K)
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Olahraga adalah STRESS !!Sel-sel otot banyak
rusakMenghabiskan
banyak energiJantung dan organ
lain harus bekerja keras
Menyisakan rasa sakit & lelah
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Ternyata !! Stress itu perluTeori Penuaan (Aging):
Sel dan komposisinya akan selalu baru bila sering di ganti !!
Untuk dapat cepat diganti Harus rusak !!!
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Olahraga StressTubuh Akan Rusak
Adaptasi Kerusakan
Hasil Lebih baik
Fisiologi Olahraga : Respon adaptasi faal tubuh terhadap perubahan homeostasis akibat stress karena olahraga
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Recovery phasesRapid recovery Late recovery
Normalization of functional activity
Normalization of homeostatic balance
Resuscitation of work capacity
Resuscitation and super compensation of energy resources
Reconstruction function
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ReconstructionPeningkatan sintesis anti oksidan sebagai
counteract radikal bebasProtein synthesis
Aktivasi hormon anabolikRepair of cell damageRe-synthesis actins-myosin
c-leucine myosin (super-compensation)
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4.2 Calorie restriction 4.2 Calorie restriction
• In the late 1980s to mid-1990s: ditemukan gen spesifik yang teraktivasi oleh retriksi kalori.
• Guarente and Sinclair menemukan gen SIR2 (encodes enzymes that stabilize DNA)
preventing abnormal DNA formation and extending life span
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4.3 Sirtuin4.3 Sirtuin
• Sirtuin or Sir2 proteins, sejenis protein yang memacu aktivitas histone deacetylase dan mono-ribosyltransferase Sirtuins mengatur transkripsi, apoptosis dan resistensi stress resistance saat terjadi retriksi kalori
• mempertahankan sel dari kerusakan
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Crystallographic structure of yeast sir2 (rainbow colored cartoon, N-terminus = blue, C-terminus = red) complexed with ADP (space-filling model, carbon = white, oxygen = red, nitrogen = blue, phosphorus = orange) and a histone H4 peptide (magenta) containing an acylated lysine residue
Crystallographic structure of yeast sir2 (rainbow colored cartoon, N-terminus = blue, C-terminus = red) complexed with ADP (space-filling model, carbon = white, oxygen = red, nitrogen = blue, phosphorus = orange) and a histone H4 peptide (magenta) containing an acylated lysine residue
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•Olahraga adalah bagian dari retriksi kalori•Olahraga lama memacu “DNA-stabilizing actions” oleh sirtuins ,
4.4 Exercise dan Sirtuin4.4 Exercise dan Sirtuin
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