Transcript Superoxide radical, O 2

Oxygen Free Radical Theory of Aging
• Oxygen is slowly killing us!
• Raj Sohal’s (Southern Methodist University)
– Has doubled or tripled the life span of house
flies if he restricts there movement and hence
the amount of oxygen they consume.
– Gene therapy can be used to increase
longevity by introducing genes that encode the
enzymes the SOD (superoxide dismutase)
and Catalase.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
-
Superoxide radical, O2 , formation
•
O2
-
•
O2
-
generated constantly as part of normal aerobic life
formed in mitochondria when O2 is reduced along the electron transport chain
Oxygen Free Radical Theory of Aging
• E.T.C. produces Superoxide Radical, O2-
– ≈10, 000 per cell per day!
– Damage DNA and membranes of mitochondria
• If you are lucky the superoxide radical is deactivated
1. SOD (superoxide dismutase) converts O2- to hydrogen
peroxide
2. Catalase converts H2O2 to water and O2
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Oxygen Free Radical Theory of Aging
If you are unlucky 
1. H2O2 moves to the nucleus of the cell
2. H2O2 reacts with Fe2+ to produce hydroxyl radical
3. Hydroxyl radical damages DNA and most
everything around it
• Hydroxyl radical causes the most damage 
4. Fe3+ can oxidize superoxide radicals back to O2
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Oxygen Free Radical Theory of Aging
• SOD and catalase levels increase when humans
exercise, thus protecting us from the extra free
radicals produced as a consequence of increased
oxygen consumption.
• House flies do not have the genes to produce
SOD and catalase consequences?
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Oxygen Free Radical Theory of Aging
1. Vitamin C (water-soluble) and Vitamin E
(fat-soluble) are vitamins that deactivate
free radicals.
2. Why might it be beneficial to take both of
them, rather than just one or the other?
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Glucose Cross-linking with Proteins
•
•
Diabetics
–
Higher than normal blood levels of glucose.
–
Causes diabetics to age ~one-third faster
Glucose is Slowly Killing Us!! 
–
Glucose reacts with proteins to form cross-links
•
Results in irreversible damage to sensitive
proteins (e.g. collagen, hemoglobin, receptors,
cell structures)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Glucose Cross-linking with Proteins
•
Cross-linking makes
proteins less flexible
–
makes body parts
less flexible and stiffer
–
major cause of aging
in many tissues:
•
skin, bones, lungs,
eyes, joints, and
blood vessels.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Glucose Cross-link