MECHANISMS OF LIFESPAN REGULATION BY SIRT6 IN DROSOPHILA MELANOGASTER - PROJECT SUMMARY: THE MAJOR GOAL OF…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG057812_075
- FAIN
- R00AG057812
- Recipient
- CLEVELAND STATE UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $736,348
- Period
- Sep 1, 2018 – Feb 28, 2026
- Fiscal year
- 2023
- Place of performance state
- OH
- Source file
- FY2023_All_Assistance_Full_20261006.zip
Description
MECHANISMS OF LIFESPAN REGULATION BY SIRT6 IN DROSOPHILA MELANOGASTER - PROJECT SUMMARY: THE MAJOR GOAL OF THIS K99/R00 PROPOSAL IS TO DETERMINE MECHANISMS BY WHICH SIRT6 REGULATES AND EXTENDS LIFESPAN. THERAPEUTIC MODULATION OF SIRT6 ACTIVITY IN HUMANS MAY BE AN EFFECTIVE WAY TO TREAT MANY AGE- RELATED DISEASES AND DISORDERS AND EXTEND HEALTHY LIFESPAN. THE ABILITY OF SIRT6 TO REGULATE LIFESPAN IN MICE HAS BEEN DEMONSTRATED, AND OUR PRELIMINARY DATA SHOW SUBSTANTIAL LIFESPAN EXTENSION BY OVEREXPRESSING THE SIRT6 DROSOPHILA MELANOGASTER ORTHOLOG, DSIRT6, IN FLIES, BUT THE EXTENT OF THIS ABILITY AND MECHANISMS BY WHICH SIRT6 OPERATES ARE POORLY UNDERSTOOD. THIS PROPOSAL WILL UTILIZE DROSOPHILA MELANOGASTER TO CLARIFY THESE ISSUES THROUGH THREE SPECIFIC AIMS. AIM 1 WILL DETERMINE WHICH TISSUES DSIRT6 ACTS THROUGH TO EXTEND LIFESPAN, AND THE RELATIVE CONTRIBUTIONS OF DSIRT6 DEACTYLASE (ASSOCIATED WITH CHROMATIN SILENCING) AND ADP-RIBOSYLASE (ASSOCIATED WITH DNA REPAIR) FUNCTIONS TOWARDS REGULATING LIFESPAN. THE RESULTS FROM THESE EXPERIMENTS SHOULD PROVIDE BETTER CONFIRMATION OF THE ABILITY OF SIRT6 TO EXTEND LIFESPAN, AND MECHANISMS BY WHICH IT OPERATES TO DO SO. AIM 2 WILL MEASURE GLOBAL GENE EXPRESSION CHANGES (RNA-SEQ) AND EPIGENOMIC ALTERATIONS (CHIP-SEQ FOR DSIRT6 SUBSTRATES H3K9AC AND H3K56AC, AND ATAC-SEQ TO LOOK AT OVERALL CHROMATIN ACCESSIBILITY) DURING AGING, WITH AND WITHOUT DSIRT6 OVEREXPRESSION. THESE RESULTS WILL PROVIDE INFORMATION ABOUT THE IMPACT OF DSIRT6 OVEREXPRESSION ON CHROMATIN DURING AGING AND THE RELATIVE IMPACT ON GENE EXPRESSION AND LIFESPAN, AND ALSO GENERAL INSIGHT INTO THE RELATIONSHIP BETWEEN AGING, CHROMATIN STATE, AND LIFESPAN. AIM 3 WILL USE BOTH TARGETED AND UNBIASED SCREENS TO IDENTIFY OTHER GENES THAT REGULATE DSIRT6 FUNCTION. THE RESULTS OF THESE EXPERIMENTS WILL PROVIDE BETTER MECHANISTIC INSIGHT INTO HOW DSIRT6 EXTENDS LIFESPAN, AND POTENTIALLY ALLOW US TO EXTEND IT EVEN FURTHER THAN WITH DSIRT6 OVEREXPRESSION ALONE. IN ADDITION