THE ROLE OF NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 IN SARCOPENIC OBESITY - PROJECT SUMMARY/ABSTRACT SA…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG083239_075
- FAIN
- R00AG083239
- Recipient
- UNIVERSITY OF OREGON
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $493,020
- Period
- Dec 1, 2023 – Jan 31, 2028
- Fiscal year
- 2025
- Place of performance state
- OR
- Source file
- FY2025_All_Assistance_Full_20261006.zip
Description
THE ROLE OF NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 IN SARCOPENIC OBESITY - PROJECT SUMMARY/ABSTRACT SARCOPENIC OBESITY IS A DEBILITATING CONDITION THAT INCREASES THE RISK OF FRAILTY, LOSS OF AUTONOMY, INSTITUTIONALIZATION, AND DEATH IN OLDER ADULTS. CURRENTLY, OBESITY MEDICATIONS AND LIFESTYLE/BEHAVIORAL INTERVENTIONS HAVE LIMITED EFFICACY FOR SARCOPENIA, WORSENING QUALITY OF LIFE, AND HEALTHSPAN. AS SUCH, THERE IS A CRITICAL NEED TO IDENTIFY AND DEVELOP TREATMENT STRATEGIES FOR PATIENTS WITH SARCOPENIC OBESITY. REACTIVE OXYGEN SPECIES (ROS) ARE LINKED WITH SEVERAL AGE-RELATED HUMAN DISEASES. OXIDATIVE STRESS HAS BEEN IMPLICATED AS A CRITICAL FACTOR CONTRIBUTING TO THE DEVELOPMENT OF SARCOPENIC OBESITY BY MEDIATING THE DECLINE IN MUSCULAR FITNESS. TO THIS END, GENETIC MANIPULATION OF REDOX SYSTEMS DRIVES OXIDATIVE STRESS, ALTERING MITOCHONDRIAL INTEGRITY AND FUNCTION IN AGED SKELETAL MUSCLE. OXIDATIVE STRESS ALSO DECREASES THE MITOCHONDRIAL NUMBER AND PHOSPHORYLATION CAPACITY WHILE INCREASING MITOCHONDRIAL DNA MUTATIONS, ULTIMATELY RESULTING IN ORGANELLE APOPTOSIS. THE NUCLEAR FACTOR ERYTHROID-RELATED 2 (NRF2) IS A PRIMARY REGULATOR OF ANTIOXIDANT AND REDOX-REGULATING PROTEIN EXPRESSION THAT MAINTAINS REDOX BALANCE ACROSS THE LIFESPAN. IN FACT, NRF2 EXPRESSION IN OLDER ADULTS IS DECREASED AND IS ASSOCIATED WITH INCREASED OXIDATIVE STRESS AND DAMAGE IN SKELETAL MUSCLE. THEREFORE, ACTIVATION OF NRF2 IS A PROMISING THERAPEUTIC APPROACH FOR SEVERAL CHRONIC DISEASES UNDER OXIDATIVE STRESS AND IMPAIRED MITOCHONDRIAL QUALITY CONTROL, SUCH AS SARCOPENIC OBESITY. THIS APPLICATION WILL EXAMINE THE ROLE OF NRF2 IN SARCOPENIC OBESITY. THE CENTRAL HYPOTHESIS IS THAT NRF2 DICTATES THE MITOCHONDRIAL QUALITY CONTROL SIGNALING, AND ITS DISRUPTION EXACERBATES MUSCLE LOSS BY IMPAIRING MITOCHONDRIAL TURNOVER AND REDOX BALANCE DURING SARCOPENIC OBESITY. IN AIM 1 (K99 PHASE), I WILL TEST WHETHER LOSS OF NRF2 REGULATES DRP1-INDUCED MITOCHONDRIAL FRAGMENTATION IN SKELETAL MUSCLE. I WI