MYONUCLEAR EPIGENETICS OF SKELETAL MUSCLE MASS REGULATION WITH AGE - PROJECT SUMMARY/ABSTRACT SKELETAL MUSC…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG063994_075
- FAIN
- R00AG063994
- Recipient
- UNIVERSITY OF ARKANSAS
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $734,641
- Period
- Aug 1, 2019 – Jul 31, 2024
- Fiscal year
- 2021
- Place of performance state
- AR
- Source file
- FY2021_All_Assistance_Full_20261006.zip
Description
MYONUCLEAR EPIGENETICS OF SKELETAL MUSCLE MASS REGULATION WITH AGE - PROJECT SUMMARY/ABSTRACT SKELETAL MUSCLE MASS DECLINES WITH AGE AND SIMULTANEOUSLY LOSES THE ABILITY TO ADAPT TO STRESSORS. REDUCED MUSCLE MASS AND FUNCTION ASSOCIATED WITH AGING ULTIMATELY LEADS TO A LOSS OF INDEPENDENCE AND MORTALITY, COSTING BILLIONS OF DOLLARS TO THE US ECONOMY EVERY YEAR. UNDERSTANDING WHAT CONTRIBUTES TO MUSCLE MASS LOSS WITH AGE AND WHAT MEDIATES THE ABILITY TO ENHANCE MUSCLE MASS WITH EXERCISE OR ALTERNATIVE THERAPEUTICS IS OF CRITICAL IMPORTANCE FOR DEVELOPING EFFECTIVE COUNTERMEASURES. THE STUDY OF EPIGENETICS, AND SPECIFICALLY DNA METHYLATION STATUS HAS BECOME INCREASINGLY POPULAR IN RECENT YEARS SINCE THIS LEVEL OF REGULATION HEAVILY DICTATES WHAT GENES ARE EXPRESSED AND FOR HOW LONG. SKELETAL MUSCLE IS MULTI-NUCLEATED AND ~50% OF NUCLEI IN THE MUSCLE COMPARTMENT ARE MYONUCLEI. LITTLE CAN BE INFERRED ABOUT DNA METHYLATION IN MUSCLE FIBERS WITHOUT THE ABILITY TO SPECIFICALLY ISOLATE MYONUCLEI. WE RECENTLY DEVELOPED A GENETICALLY MODIFIED MOUSE MODEL FOR LABELING SKELETAL MUSCLE MYONUCLEI AND A WORKFLOW FOR PURIFYING THESE LABELED MYONUCLEI FOR DOWNSTREAM EPIGENETIC APPLICATIONS. WE ALSO DEVELOPED A TRANSLATABLE AND REVERSIBLE MURINE MODEL OF PROGRESSIVE WEIGHTED WHEEL RUNNING (POWER) THAT ELICITS HYPERTROPHY IN MUSCLES OF DIFFERENT FIBER TYPE COMPOSITION AND FUNCTION. USING THESE NOVEL TOOLS, THE PURPOSE OF THIS PROPOSAL IS TO PROVIDE THE FIRST MUSCLE TYPE-SPECIFIC INSIGHT INTO THE EPIGENETIC REGULATION OF SKELETAL MUSCLE MASS WITH AGING, AND DETERMINE WHETHER EARLY LIFE STIMULI AFFECT MUSCLE ADAPTABILITY LATER IN LIFE. I WILL PROFILE MYONUCLEAR DNA USING REDUCED REPRESENTATION BISULFITE SEQUENCING IN ORDER TO EXPLORE GLOBAL METHYLATION STATUS, AND FOCUS IN ON RIBOSOMEAL DNA (RDNA) METHYLATION SINCE RIBOSOME BIOGENESIS IS STRONGLY IMPLICATED IN SKELETAL MUSCLE MASS REGULATION. IN THE MENTORED PHASE OF THE GRANT, I WILL LEARN THE REQUISITE EPIGENETIC TECHNIQUES FOR STUDYI