REVERSING AGE-RELATED EPIGENETIC CHANGES AND CHARACTERIZING MICROGLIA HETEROGENEITY IN OBESITY AND AGING -…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
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ASST_NON_K00AG079813_075 · UNIVERSITY OF SOUTHERN CALIFORNIA · Department of Health and Human Services
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- Assistance award identifier
- ASST_NON_K00AG079813_075
- FAIN
- K00AG079813
- Recipient
- UNIVERSITY OF SOUTHERN CALIFORNIA
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $234,621
- Period
- Dec 1, 2022 – Jan 31, 2028
- Fiscal year
- 2024
- Place of performance state
- CA
- Source file
- FY2024_All_Assistance_Full_20261006.zip
Description
REVERSING AGE-RELATED EPIGENETIC CHANGES AND CHARACTERIZING MICROGLIA HETEROGENEITY IN OBESITY AND AGING - PROJECT SUMMARY NEUROINFLAMMATION IS A HALLMARK OF BRAIN AGING THAT MAY CONTRIBUTE TO DECLINES IN FUNCTION AND NEURODEGENERATIVE DISEASES. AS THE RESIDENT MACROPHAGE OF THE BRAIN, MICROGLIAL ARE CRUCIAL TO BRAIN MAINTENANCE BUT HAVE BEEN DEMONSTRATED TO TAKE ON PRO-INFLAMMATORY PHENOTYPES WITH AGING. THE PROPOSED RESEARCH WILL EXAMINE THE ROLE OF MICROGLIA-SPECIFIC EPIGENETIC MECHANISMS IN AGING AND DETERMINE THE EFFECTS OF OBESITY AND AGING INTERACTIONS ON MICROGLIA PHENOTYPIC HETEROGENEITY. WE WILL DETERMINE WHETHER ABERRANT AGE-RELATED MICROGLIA-SPECIFIC EPIGENETIC PATTERNS CAN BE REVERSED BY HETEROCHRONIC PLASMA APPROACHES. ADDITIONALLY, WE WILL DETERMINE HOW MICROGLIA SUBPOPULATIONS DIFFER WITH AGE AND OBESITY AT A SINGLE-CELL LEVEL WITH SPECIAL INTERESTS IN LIPID-DROPLET- ACCUMULATING MICROGLIA (LDAM). THE GOALS OF THE TRAINING ARE TO: 1) OBTAIN A STRONG KNOWLEDGE AND FOUNDATION IN ANIMAL AND NUTRITIONAL MODELS OF ANTI-AGING AND OBESITY 2) GAIN HANDS-ON EXPERIENCE IN TECHNOLOGIES AND BIOINFORMATIC SKILLS NEEDED FOR VARIOUS OMICS APPROACHES IN SPECIFIC HIPPOCAMPAL CELLS AND AT A SINGLE-CELL LEVEL 3) APPLY THESE SKILLS TO ACHIEVE THE RESEARCH AIMS OUTLINED IN THIS PROPOSAL AND 5) GAIN EXPERIENCE AND IMPROVE ORAL AND PRESENTATION SKILLS, MANUSCRIPT AND GRANT WRITING TO ENABLE A TRANSITION TO INDEPENDENCE. IN AIM 1, WE HYPOTHESIZE THAT EXPOSURE OF OLD MICE TO YOUNG PLASMA WILL REVERSE AGE-RELATED MICROGLIA-SPECIFIC DNA MODIFICATIONS TO RESTORE âYOUTHFULâ EPIGENOMIC PATTERNS. THIS IS BASED ON THE PREMISE THAT DNA MODIFICATIONS ARE KEY REGULATORS OF THE DIVERSE PHENOTYPES REQUIRED FOR THE FULFILLMENT OF MICROGLIA FUNCTIONS WHICH ARE DISRUPTED IN AGING. WE WILL DETERMINE WHETHER THE ADMINISTRATION OF PLASMA FROM YOUNG INTO OLD MICE CAN REVERSE AGE-RELATED MICROGLIAL-SPECIFIC HIPPOCAMPAL EPIGENETIC AND TRANSCRIPTOMIC CHANGES IN CX3CR1:NUTRAP MICE USING WHOLE