MUSCLE AND BONE GROWTH IN AGING - PROJECT SUMMARY/ABSTRACT SKELETAL MUSCLE AND BONE INTEGRITY PROGRESSIVELY…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG068438_075
- FAIN
- K00AG068438
- Recipient
- TRUSTEES OF INDIANA UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $347,913
- Period
- Sep 15, 2021 – Aug 31, 2026
- Fiscal year
- 2022
- Place of performance state
- IN
- Source file
- FY2022_All_Assistance_Full_20261006.zip
Description
MUSCLE AND BONE GROWTH IN AGING - PROJECT SUMMARY/ABSTRACT SKELETAL MUSCLE AND BONE INTEGRITY PROGRESSIVELY DECLINES AS WE AGE, LARGELY DUE TO DECREASED LEVELS OF GROWTH FACTORS AND PHYSICAL ACTIVITY. INSULIN-LIKE GROWTH FACTOR-I (IGF-I) IS A MAJOR MEDIATOR OF MUSCLE GROWTH AND REGENERATION, SPECIFICALLY THROUGH THE REGULATION OF MUSCLE STEM CELLS (SATELLITE CELLS) IN ORDER TO REPAIR DAMAGED MUSCLE FIBERS. DURING AGING, THE GRADUAL DECREASE IN IGF-I LEVELS CONTRIBUTES TO THE FAILURE OF THE MUSCLE GROWTH AND REGENERATIVE CAPACITY FURTHER CAUSING LOSS OF MUSCLE MASS AND FUNCTION; HOWEVER, WHICH CELL IN THE MUSCLE PROVIDES THE CRITICAL SOURCE OF IGF-I HAVE YET TO BE ESTABLISHED. THUS, AIM 1 OF THIS FELLOWSHIP IS TO DETERMINE THE CRITICAL SOURCE OF IGF-I IN THE MUSCLE MILIEU THAT PROMOTES MUSCLE GROWTH AND REGENERATION, WITH NOVEL MOUSE MODELS THAT ABLATE CELL-SPECIFIC IGF-I PRODUCTION, DEVELOPED BY THE PI. THE HYPERTROPHIC RESPONSE OF THE MUSCLE BEDS FROM IGF-I HAS THE POTENTIAL TO PROVIDE THE BENEFITS OF MECHANICAL LOADING TO THE BONE. INDEED, MUSCULAR CONTRACTION FACILITATES MECHANICAL STIMULATION TO THE BONE; HOWEVER, PHYSICAL INACTIVITY IN THE AGING POPULATION DECREASES THE ABILITY OF BONES TO SENSE AND RESPOND TO MECHANICAL FORCES, WHICH CONTRIBUTES TO THE DECLINE IN BONE DENSITY AND STRENGTH. OSTEOCYTES ARE MATURE BONE CELLS THAT SENSE AND RESPOND TO MECHANICAL STIMULI FROM THE MUSCLE, FURTHER DIRECTING THE ACTIVITY OF OSTEOCLASTS (BONE RESORPTION) AND OSTEOBLASTS (BONE FORMATION) FOR BONE REMODELING. PERLECAN (PLN) IS ESSENTIAL FOR OSTEOCYTE MECHANOTRANSDUCTION; HOWEVER, PLN AVAILABILITY DECREASES WITH AGE DUE TO DECREASED MECHANOTRANSDUCTION. NONETHELESS, THE EFFECTS OF BONE REMODELING DUE TO DECREASED PLN EXPRESSION IN THE OSTEOCYTIC MATRIX REMAINS UNKNOWN. ADDITIONALLY, PLN IS KNOWN TO SEQUESTER NUMEROUS GROWTH FACTORS; HOWEVER, WHETHER PLN SERVES AS A GROWTH FACTOR RESERVOIR TO INDUCE BONE FORMATION IS ENTIRELY UNEXPLORED. THEREFORE, AIM 2 OF THIS PROPOSAL I