1. arNOX, AGING-RELATED CELL SURFACE ECTO-NOX PROTEIN D. James Morré and Dorothy Morré Department of Medicinal Chemistry & Molecular Pharmacology and Department of Foods and Nutrition Purdue University, W. Lafayette, Indiana 47907

2. Preventative target to reduce atherogenic risk in the elderly

3. NOX Quinone Reductase Q 10 Q 10 H 2 1/2 O 2 H2OH2O NAD(P)H + H + NAD(P) + Protein S S Outside Inside Plasma Membrane 2 O 2 - SH

4. Glucose Pyruvate ATP NADH + H + ADP Glycolysis NAD + + Mitochondrial DNA mutations Anaerobic Cell ATP Production by Glycolysis Enhanced PMOR Activity to Oxidize NADH Propagation of Response LDL oxLDL Atherosclerosis Glucose Pyruvate NADH + H + + Glycolysis NAD + AH 2 A PMOR 2 H + + 2 e - - 2 1/2 O 2 HO Generation of ROS at PM. O 2 - H 2 O 2 OH Adjacent cells

5. SOD – inhibited reduction of ferricytochrome c Human (Age > 50y) –Buffy coats –Sera –Saliva –Perspiration Late-passage cell culture –MCF-10A –WI-38 Plants –Senescent spinach leaves –Senescent Aracean spathes

6. Ferricytochrome c reduction Human20 – 40y50 – 70y nmoles/min/10 6 cells Buffy coats +SOD 0.02.06.02 nmoles/min/ml Sera +SOD 0.1 0.3 0.1 Saliva +SOD 0.15 0.1 0.5 0.1 nmoles/min/Osteopatch Perspiration +SOD 0.03 0.3 0.03 Morré, D.M, F. Guo and Morré, D.J. 2003 Mol. Cell. Biochem. 254:101-109.

7. Coenzyme Q (Q 8, Q 9 and Q 10 but not by Q 0, Q 2, Q 4, or Q 7 ) Several Chinese botanicals with antiaging activities Morré, D.M and Morré, D.J. 2003 BioFactors 18:33-43 Buffy Coats Ar NOX inhibited by

8. Summary Aging-related NOX Generates superoxide Cells and sera of aged individual (>50y) Postulated to propagate aging cascade to adjacent cells and circulating lipoproteins Ablated by coenzyme Q 10 /Antiaging botanicals