Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof

Abstract

The invention described herein encompasses methods of preventing or treating disorders caused by oxidative damage by an aging-specific isoform of NADH oxidase (AR—NOX). The invention encompasses methods of assaying, screening, and identifying agents that inhibit AR—NOX, as well as methods using ubiquinone to inhibit the ability of AR—NOX to generate reactive oxygen species. These agents may be formulated into pharmaceutical compositions in the prevention and treatment of disorders caused by oxidative damage.

1 . A method of preventing a complication of a primary disorder in patients wherein said complication results from oxidative damage resulting from the generation of reactive oxygen species by AR—NOX, which comprises: 
 administering to a patient having said primary disorder, in an amount effective to prevent said complication, one or more ubiquinones in a pharmaceutically acceptable carrier.    
     
     
         2 . A method for preventing secondary disorders in patients having a primary disorder that causes oxidative damage resulting from the generation of reactive oxygen species by AR—NOX which comprises: 
 administering to a patient having a primary disorder, in an amount effective to prevent said secondary disorder, one or more ubiquinones in a pharmaceutically acceptable carrier.    
     
     
         3 . The method of  claim 1  or  2  wherein the total daily amount of ubiquinones administered is from about 1 to about 500 mg of a composition comprising ubiquinones.  
     
     
         4 . The method of  claim 3  wherein the total daily amount of ubiquinones administered is from 1 to 100 mg of the compositions comprising ubiquinones.  
     
     
         5 . The method of  claim 1  or  2  wherein the ubuqionone is coenzyme Q 10 .  
     
     
         6 . The method of  claim 1  or  2  wherein said ubiquinone is not coenzyme Q 10 .  
     
     
         7 . The method of  claim 1  or  2  wherein coenzyme Q 10  is administered with a ubiquinone selected from a group consisting of coenzyme Q 6 , coenzyme Q 7 , coenzyme Q 8 , or coenzyme Q 9 .  
     
     
         8 . The method of  claim 1  or  2  wherein the primary disorder is old age, rheumatoid arthritis, arthritis associated with age, or fatigue associated with age.  
     
     
         9 . The method of  claim 1  or  2  wherein the primary disorder is a result of aged cells.  
     
     
         10 . The method of  claim 1  or  2  wherein the primary disorder is cancer.  
     
     
         11 . The method of  claim 1  or  2  wherein the primary disorder is selected from a group comprising myocardial infarction, alcoholism, favism, malaria, sickle cell anemia, Fanconi's anemia, protoporphyrin photo-oxidation, nutritional deficiencies, Kwashiorkor, thalassemia, dietary iron overload, idiopathic hemochromatosis, metal ion-mediated nephrotoxicity, aminoglycoside nephrotoxicity, autoimmune nephrotic syndromes, oral iron poisoning, endotoxin liver injury, free fatty acid-induced pancreatitis, nonsteroidal antiinflammatory drug induced gastrointestinal tract lesions, glomerulonephritis, autoimmune diseases, vasculitis, hepatitis B virus, Parkinson's disease, neurotoxins, allergic encaphalomyelitis, potentiation of traumatic injury, hypertensive cerebrovascular injury, vitamin E deficiency, adriamycin cardiotoxicity, Keshan disease, selenium deficiency, alcohol cardiomyopathy, photic retinopathy, occular hemorrhage, cataractogenesis, degenerative retinal damage, amyotrophic lateral sclerosis, aged-related macular degeneration, diabetes, atherogenesis, and atherosclerosis.  
     
     
         12 - 54 . (canceled)