Reduced skeletal loading leads to muscle atrophy and bone loss in humans and most mammals. Disuse muscle atrophy and osteoporosis represent significant clinical problem for patients during prolonged periods of immobilization and bed rest. Bears and ground squirrels are largely inactive during hibernation, but they show no loss in bone mass and less muscle atrophy than would be anticipated over such a prolonged period of physical inactivity. This suggests that hibernating mammals have unique natural adaptation to musculoskeletal disuse. Although preservation of bone mass and attenuation of muscle atrophy in hibernating bears and ground squirrels have been documented, molecular mechanisms underlying this important adaptation are not known. Our goal is to identify through transcriptional changes physiologically relevant candidate pathways and understand molecular mechanisms preventing disuse muscle atrophy and bone loss in hibernating mammals. Advantage of the next generation sequencing tools will be used to conduct large scale screens of transcriptional changes in bone and muscle comparing winter hibernating and summer active animals. Genome-wide transcriptional profiling will detect sufficiently large number of differentially expressed genes for comprehensive pathway analysis elucidating functional significance of transcriptional changes. Comparison of functional gene groups and pathways enriched by co regulated genes between two evolutionary distant species with different hibernation modes is expected to reveal general transcriptional program with untapped potential for development of improved treatment and prevention of disuse muscle atrophy and osteoporosis in non-hibernating mammals, including humans. .

Public Health Relevance

Disuse muscle atrophy and osteoporosis represent significant health problem. Hibernating mammals demonstrate unique ability to reduce muscle atrophy and prevent bone loss during physical inactivity in winter. Our research to identify through transcriptional profiling molecular mechanisms that underlie this natural adaptation to disuse will provide novel insights with potential for development of improved treatment and prevention of muscle atrophy and osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR064995-01A1
Application #
8700761
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Sharrock, William J
Project Start
2014-04-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$198,000
Indirect Cost
$66,000
Name
University of Alaska Fairbanks
Department
None
Type
Organized Research Units
DUNS #
615245164
City
Fairbanks
State
AK
Country
United States
Zip Code
99775
Fedorov, Vadim B; Goropashnaya, Anna V; Stewart, Nathan C et al. (2014) Comparative functional genomics of adaptation to muscular disuse in hibernating mammals. Mol Ecol 23:5524-37