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.

Description

[0001]This application claims the benefit of U.S. Provisional Application No. 60 / 298,506, filed Jun. 15, 2001, the contents of which are hereby incorporated by reference into this application.BACKGROUND OF THE INVENTION[0002]The p53 tumor suppressor exerts anti-proliferative effects, including growth arrest, apoptosis, and cell senescence, in response to various types of stress (Levine, 1997; Prives and Hall, 1999; Vogelstein et al., 2000). Mutations within the p53 gene have been well documented in more than half of all human tumors (Hollstein et al., 1994). Accumulating evidence further indicates that, in the cells that retain wild-type p53, other defects in the p53 pathway also play an important role in tumorigenesis (Prives and Hall, 1999; Lohrum and Vousden, 1999). The molecular function of p53 that is required for tumor suppression involves its ability to act as a transcriptional factor in regulating downstream target gene expression (reviewed in Nakano and Vousden, 2001; Yu et...

AI Technical Summary

Benefits of technology

[0014]This invention further provides 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.

[0015]This invention further provides a method for prolonging the life-span of a subject 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 prolonging the subject's life-span.

[0016]This invention further provides 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.

[0017]This invention still further provides a method for prolonging the life-span of a cell 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 prolonging the life-span of the cell.

[0019]The second article of manufacture comprises a packaging material and an agent contained therein that increases the amount of Sir2α in a cell and / or the ability of Sir2α to inhibit p53-dependent apoptosis in a cell, and a label indicating that the agent is used for decreasing the amount of damage to a subject's cells caused by physical stress, prolonging the life-span of a subject, decreasing the amount of damage to a cell caused by physical stress, and / or prolonging the life-span of a cell.

Problems solved by technology

However, their biological functions remain unclear.

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