ELUCIDATING THE MECHANISMS OF TRANSLATIONAL APPROACHES TO ENHANCE RECOVERY OF AGED MUSCLE - PROJECT SUMMARY…

Assistance award details

Assistance award identifier

ASST_NON_K00AG073493_075

FAIN

K00AG073493

Recipient

DANA-FARBER CANCER INSTITUTE, INC.

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$320,209

Period

Sep 15, 2021 – Aug 31, 2027

Fiscal year

2023

Place of performance state

MA

Source file

FY2023_All_Assistance_Full_20261006.zip

Description

ELUCIDATING THE MECHANISMS OF TRANSLATIONAL APPROACHES TO ENHANCE RECOVERY OF AGED MUSCLE - PROJECT SUMMARY/ABSTRACT MUSCLE ATROPHY RESULTING FROM PHYSICAL DISUSE (SUCH AS POST-SURGERY, OR WITH EXTENDED PERIODS OF PHYSICAL INACTIVITY) INCREASES FALL RISK AND DISABILITY IN OLDER ADULTS. WITH A GROWING AGING POPULATION, THE DYSFUNCTIONS RELATED TO PHYSICAL DISUSE WILL BE WIDESPREAD CONTRIBUTING TO LARGE-SCALE DECREASES IN HEALTHSPAN, AND INCREASES IN MORBIDITIES AND HOSPITALIZATIONS AS SKELETAL MUSCLE HEALTH IS IMPORTANT FOR WHOLE BODY GLUCOSE REGULATION, POSTURAL STABILITY/BALANCE, AND STRENGTH TO PERFORM ACTIVITIES OF DAILY LIVING (INDEPENDENCE). UNFORTUNATELY, PHYSICAL REHABILITATION ALONE DOES NOT ALWAYS ADEQUATELY RESTORE MUSCLE SIZE AND FUNCTION IN OLDER POPULATIONS. THE USE OF MECHANISTIC-BASED, TRANSLATIONAL THERAPEUTICS MAY PROVIDE A MUCH-NEEDED SOLUTION TO IMPROVE MUSCLE RECOVERY IN OLDER ADULTS FOLLOWING DISUSE, HOWEVER, WELL DESIGNED, TRANSLATIONAL PRE-CLINICAL TRIALS TESTING THERAPEUTIC AGENTS ARE REQUIRED. HERE, IN THE F99 PHASE, I PROPOSE A RIGOROUS PRE-CLINICAL TRIAL UTILIZING A METFORMIN AND LEUCINE COMBINATION TREATMENT (MET+LEU) TO PROMOTE MUSCLE RECOVERY FROM DISUSE IN AGED MICE. MY CURRENT PROGRESS SUPPORTS THAT MET+LEU PROMOTES RECOVERY FROM DISUSE IN AGED MICE AS EVIDENCED BY INCREASED STRENGTH, SATELLITE CELLS AND REDUCED MUSCLE FIBROSIS. THROUGH IN VITRO AND IN VIVO METHODS, WE AIM TO TEST THE MECHANISM OF MET+LEU ACTION. THE GOAL OF THIS WORK IS TO IDENTIFY IF MET+LEU TREATMENT CONFERS POSITIVE BENEFITS IN A SKELETAL MUSCLE CELL AUTONOMOUS FASHION, AND IF THE EFFECTS OF MET+LEU ARE REGULATED THROUGH THE SIRT1-AMPKA-PGC-1A SIGNALING AXIS, IMPLICATED TO BE TARGETED BY MET+LEU. DURING THE K00 PHASE, I WILL WORK UNDER AN EXPERT IN MUSCLE AGING SPECIFICALLY IN EXTRACELLULAR MATRIX REMODELING AND FIBROBLAST- SATELLITE CELL CROSSTALK, TO FURTHER ELUCIDATE THE EFFECTS OF MET+LEU AND OTHER TRANSLATIONAL THERAPEUTICS ON MUSCLE HEALTH. IN DOING SO, WE W