Compositions for manipulating the lifespan and stress response of cells and organisms

Abstract

Provided herein are methods and compositions for modulating the activity of sirtuin deacetylase protein family members; p53 activity; apoptosis; lifespan and sensitivity to stress of cells and organisms. Exemplary methods comprise contacting a cell with an activating compound, such as a flavone, stilbene, flavanone, isoflavone, catechin, chalcone, tannin or anthocyanidin; or an inhibitory compound, such as a sphingolipid, e.g., sphingosine.

1 . A method for mimicking the effects of calorie restriction in a eukaryotic cell, comprising contacting the cell with a compound having a formula selected from the group consisting of formulas 32-65.  
     
     
         2 . The method of  claim 1 , wherein the compound is a compound set forth in Table 21 of  FIG. 35 .  
     
     
         3 . The method of  claim 1 , wherein the cell is in vitro.  
     
     
         4 . The method of  claim 1 , wherein the cell is a mammalian cell.  
     
     
         5 . The method of claim  16 , wherein the cell was obtained from a subject.  
     
     
         6 . The method of  claim 1 , wherein the cell is a yeast cell.  
     
     
         7 . A method for treating an aging-related disease in a subject, comprising administering to a subject in need thereof, a therapeutically effective amount of an agent of  claim 1 .  
     
     
         8 . The method of claim  27 , wherein the aging-related disease is stroke, a cardiovascular disease, arthritis, high blood pressure, or Alzheimer's disease.  
     
     
         9 . A method for reducing the lifespan of a eukaryotic cell or rendering the eukaryotic cell more sensitive to cell death, comprising contacting the cell with a compound having a formula selected from the group consisting of formulas 67-68.  
     
     
         10 . The method of  claim 9 , wherein the compound is a compound set forth in Table 22 of  FIG. 36 .  
     
     
         11 . A method for treating a disease or condition related to abnormal cell growth in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an agent of  claim 9 .  
     
     
         12 . The method of  claim 11 , wherein the disease or condition is cancer.  
     
     
         13 . The method of  claim 12 , further comprising administering to the subject a chemotherapeutic agent.  
     
     
         14 . A composition comprising two compounds having a formula selected from the group consisting of formulas 32-65 and 67-68, wherein the composition is not a composition in which the two compounds are naturally present together.