Sir2a-based therapeutic and prophylactic methods

Abstract

This invention provides methods for treating and for inhibiting the onset of cancer in a subject comprising administering an agent that inhibits the ability of Sir2α to inhibit p53-dependent apoptosis. This invention also provides a related method for inducing the death of a cell. This invention further provides a method for decreasing the amount of damage to a subject's cells caused by physical stress comprising administering agent that increases the amount of Sir2α in the subject's cells and/or the ability of Sir2α to inhibit p53-dependent apoptosis in the subject's cells. This invention further provides related methods for prolonging the life-span of a subject, decreasing the amount of damage to a cell caused by physical stress, and prolonging the life-span of a cell. Finally, this invention provides two articles of manufacture for performing the instant methods.

1 . A method for treating a subject afflicted with cancer comprising administering to the subject a therapeutically effective amount of an agent that inhibits the ability of Sir2α to inhibit p53-dependent apoptosis, thereby treating the subject. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the subject is a human. 
     
     
         4 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , further comprising administering to the subject an agent that enhances p53-dependent apoptosis via a mechanism other than Sir2α inhibition. 
     
     
         7 - 15 . (canceled) 
     
     
         16 . A method for decreasing the amount of damage to a subject's cells caused by physical stress comprising administering to the subject a prophylactically effective amount of an agent that increases the amount of Sir2α in the subject's cells and/or the ability of Sir2α to inhibit p53-dependent apoptosis in the subject's cells, thereby decreasing the amount of damage to the subject's cells. 
     
     
         17 . The method of  claim 16 , wherein the damage is selected from a group consisting of DNA damage and membrane damage. 
     
     
         18 . The method of  claim 16 , wherein the physical stress is selected from the group consisting of ultraviolet radiation and oxidation. 
     
     
         19 . The method of  claim 16 , wherein the agent is administered prior to and/or concurrently with the occurrence of the physical stress. 
     
     
         20 . The method of  claim 16 , wherein the agent is administered subsequent to the occurrence of physical stress. 
     
     
         21 - 23 . (canceled) 
     
     
         24 . A method for decreasing the amount of damage to a cell caused by physical stress comprising contacting the cell with an agent that increases the amount of Sir2α in the cell and/or the ability of Sir2α to inhibit p53-dependent apoptosis in the cell, thereby decreasing the amount of damage to the cell. 
     
     
         25 . The method of  claim 24 , wherein the damage is selected from the group consisting of DNA damage and membrane damage. 
     
     
         26 . The method of  claim 24 , wherein the physical stress is selected from the group consisting of ultraviolet radiation and oxidation. 
     
     
         27 . The method of  claim 24 , wherein the cell is contacted with the agent prior to and/or concurrently with the occurrence of the physical stress. 
     
     
         28 . The method of  claim 24 , wherein the cell is contacted with an agent subsequent to the occurrences of the physical stress. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 24 , wherein the cell is a human cell. 
     
     
         31 . The method of  claim 24 , wherein the agent is a Sir2α-encoding nucleic acid. 
     
     
         32 - 33 . (canceled)