Osteocyte Regulation of Bone/Muscle with Age

  • Esser, Karyn (PI)

Grants and Contracts Details


Osteoporosis and Sarcopenia are major clinical problems in the aging population and in many patients these two conditions occur concurrently. This combination results in instability, susceptibility to falls and consequently to fracture, morbidity, and premature death. It is unclear whether one condition precedes the other or if the conditions are linked. We have proposed that soluble factors are produced by each tissue with exercise acting to maintain optimal tissue structure and function and that the profile of secreted factors changes with aging. It has been well established that aging is associated with significant changes in the circadian output including decreased clock stability and phase shifts that lead to increased mis-alignment of the phases among the clocks in the body. Aging is also associated with decreased amplitude of the rhythms. A mouse model has been generated where a specific clock gene called Bmal, known to control circadian rhythm, is deleted in muscle. These mice demonstrated reductions in both maximal force and passive tension properties with no loss in muscle mass. They also exhibited characteristics of accelerated aging. Surprisingly, these mice also exhibitdc a skeletal phenotype that is distinctly different and not seen in models of muscular dystrophies suggesting crosstalk between the defective muscle and bone. Our hypothesis is that the defective muscle is no longer producing factors necessary for the maintenance of healthy bone. In this supplement, we propose to characterize the skeletal phenotype to provide the basis for future studies to identify the molecular mechanisms responsible for the skeletal phenotype and the advanced aging.
Effective start/end date9/15/144/30/15


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.