1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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.

2. Superoxide radical, O 2 -, formation O 2 - generated constantly as part of normal aerobic life O 2 - formed in mitochondria when O 2 is reduced along the electron transport chain

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Oxygen Free Radical Theory of Aging E.T.C. produces Superoxide Radical, O 2 - – ≈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 O 2 - to hydrogen peroxide 2.Catalase converts H 2 O 2 to water and O 2

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Oxygen Free Radical Theory of Aging If you are unlucky  1.H 2 O 2 moves to the nucleus of the cell 2.H 2 O 2 reacts with Fe 2+ to produce hydroxyl radical 3.Hydroxyl radical damages DNA and most everything around it Hydroxyl radical causes the most damage  4.Fe 3+ can oxidize superoxide radicals back to O 2

5. 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?

6. 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?

7. 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)

8. 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. Glucose Cross-link