INVESTIGATING TFEB AS A CRITICAL NODE TO IMPROVE PROTEOSTATIC MAINTENANCE AND SKELETAL MUSCLE FUNCTION WITH…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG086524_075
- FAIN
- R00AG086524
- Recipient
- UNIVERSITY OF OKLAHOMA
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $249,000
- Period
- Dec 1, 2024 – Aug 31, 2029
- Fiscal year
- 2026
- Place of performance state
- OK
- Source file
- FY2026_All_Assistance_Full_20261006.zip
Description
INVESTIGATING TFEB AS A CRITICAL NODE TO IMPROVE PROTEOSTATIC MAINTENANCE AND SKELETAL MUSCLE FUNCTION WITH AGE - PROJECT SUMMARY/ABSTRACT SKELETAL MUSCLE ATROPHY AND DYSFUNCTION ARE A HALLMARK OF AGING, SARCOPENIA, AND DISUSE ATROPHY THAT SIGNIFICANTLY AFFECT INDIVIDUAL HEALTH SPAN AND QUALITY OF LIFE. THERE ARE CURRENTLY NO EFFECTIVE TREATMENTS FOR AGE RELATED MUSCLE DYSFUNCTION BECAUSE UNDERLYING MECHANISMS THAT CONTRIBUTE TO MUSCLE PATHOLOGY ARE NOT FULLY UNDERSTOOD. A RECENTLY PUBLISHED MANUSCRIPT FROM THE PI SHOWS THAT PROTEIN SYNTHESIS AND MTOR ACTIVITY, A PRIMARY REGULATOR OF PROTEIN SYNTHESIS, IS HIGH IN AGED MUSCLE, LIKELY INHIBITING TFEB (TRANSCRIPTION FACTOR EB) NUCLEAR TRANSLOCATION AND SUBSEQUENT ACTIVITY. THIS FINDING SUGGESTS THAT IMPAIRED PROTEIN DEGRADATION, NOT PROTEIN SYNTHESIS, COMPROMISES MAINTENANCE AND RECOVERY OF AGED MUSCLE. WE ALSO SHOWED THAT THERE WAS AN ACCUMULATION OF INSOLUBLE UBIQUITINATED PROTEINS AND P62 PROTEIN IN THE INSOLUBLE FRACTION OF OLD MUSCLE. TOGETHER, THESE DATA SUGGEST THAT COMPROMISED AUTOPHAGY DEPENDENT PROTEIN DEGRADATION LIKELY IMPACTS SKELETAL MUSCLE FUNCTION IN AGED MUSCLE WITH SARCOPENIA AND RECOVERY AFTER DISUSE ATROPHY. THE GOAL OF THIS PROJECT IS TO DETERMINE IF TFEB FUNCTIONS AS A CRITICAL NODE IN MUSCLE MAINTENANCE WITH SARCOPENIA AND RECOVERY WITH DISUSE ATROPHY IN AGED MUSCLE. TFEB STIMULATES LYSOSOMAL BIOGENESIS AND AUTOPHAGY, WHICH ARE ESSENTIAL IN TARGETED PROTEIN DEGRADATION AND THEREFORE PROTEOSTATIC MAINTENANCE. THE HYPOTHESIS OF THIS PROPOSAL IS THAT TFEB FUNCTIONS AS A CRITICAL NODE TO IMPROVE MAINTENANCE AND RECOVERY OF SKELETAL MUSCLE MASS AND FUNCTION WITH AGING IN TWO CONDITIONS OF MUSCLE DYSFUNCTION, SARCOPENIA AND DISUSE ATROPHY. THE FOLLOWING SPECIFIC AIMS ARE PROPOSED TO TEST THE HYPOTHESIS: AIM 1: DETERMINE IF INCREASING TFEB ACTIVITY IMPROVES MAINTENANCE OF MUSCLE MASS AND FUNCTION IN AGED MICE. AIM 2: DETERMINE IF MTOR ACTIVITY REGULATES TFEB-DEPENDENT PRESERVATION OF PROTEOSTATIC MAINT