Biokimia

Proses Penuaan

Oxidative Damage

Aging
 Oxidative Damage

Oksidoreduktase Trasnfer Elektron

Mitokondria Energi (ATP)

Fosforilasi Oksidatif
Oxidoreduktase

1. Oxidase

2. Dehidrogenase

3. Hydroperoxidase

4. Oxigenase
1. Oxidase

Melepas 2 proton (H+) dari substrat dan

digabungkan dengan oksigen

Menghasilkan H2O atau H2O2

 3. Hydroperoxidase

Peroxidase
Mengubah peroxide (H2O2) menjadi air (H2O)
dengan menggunakan substrat
Katalase
Mengubah peroxide menjadi air (H2O) tanpa substrat
 3. Hydroperoxidase

Reaksi Peroksidase

Reaksi Katalase
Peran Oksigen pada Kerusakan Sel
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Reactive Oxygen Species (ROS) are oxygen radicals damage to cells and tissues,
such as in :
- Neurodegenerative diseases Alzheimer, Parkinson.
- Cardiovascular diseases
- Rheumatoid Arthritis (RA) Bone erosion, cartilage loss, loss of joint function.

Effect of ROS on :
a. Lipid and Nucleic Acids easy target for oxidative
damage (lipid peroxidation)
b. Cellular protein and Enzymes Oxidation produces altered proteins

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Altered proteins accumulate with aging will interfere with normal homeostasis
cause age related pathologies, such as :
- Atherosclerosis
- Senile cataract
- Immune system failure
- Neurodegenerative diseases

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Age related changes in enzymes and other proteins :
- Alteration in catalytic activities
- Altered folding in the 3-D structure

With aging Disturbed balance between accumulation and degradation of

modified forms.

Other type of age associated modification:

- Protein Glycosylation non enzymatic

Causes aging of long lived proteins Collagen & Crystallin

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- Inactivation by glycosylation occurs in proteins with lysine in critical location
- Experimentally inactivated when incubated in glucose
- Final products of glycosylaton called Advanced Glycosylation Endproducts (AGE)
- Free radicals induce formation and accumulation of AGE

ANTIOXIDANTS inhibit protein glycation and accumulation of AGE

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With increasing age and glucose concentration :
accumulation of AGE in plasma and vessel walls
cause many diabetic complications cataract, atherosclerosis

Other type of protein modification due to oxidative stress formation of

protein-protein Cross Links caused mainly by disulfide bonds

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Mitochondrial Dysfunction ROS generated during aging Chronic oxidative
damage to Electron Transport System (ETS)

Resulting decrease in functional capacity of cells and tissues during aging

Caloric Restriction (CR) Since major endogenous source of ROS

is mitochondrial respiration, CR markedly reduces production of Superoxide and H2O2
Effect of CR most striking in brain

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Kristal and Yu (1992) Age related deterioration is produced by the sum
of the damage induced by free radicals, by glycation (Maillard reaction)
and by their interactions.

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