Stem Cell Loss and Skeletal Muscle Decline
Based on lineage tracing and depletion studies, it is clear resident stem cells do contribute to the lifelong maintenance of skeletal muscles. However, the mechanisms whereby resident stem loss leads to skeletal muscle atrophy and dysfunction is unknown. Moreover, the stimuli that evoke resident stem cell activation and contribution to intact skeletal muscle in relatively sedentary adult organisms are unclear.
Sprouty1 and Stem Cell Maintenance
Sprouty1, a receptor tyrosine kinase feedback regulator, is a critical regulator of skeletal muscle resident stem cell fate. However, the factors that regulate sprouty1 expression and signaling are ill-defined.
Skeletal Muscle Decline in Juvenile Cancer Survivors
Although estimates indicate the 5-year survival rate of children diagnosed with a malignancy is near 80%, the vast majority of these individuals prior to age of 40 demonstrate indices of physical limitation normally associated with the elderly population. Among the age-related phenotypes observed earlier in childhood cancer survivors is the accelerated loss of lean body skeletal muscle tissue and strength with age. Despite these observations the cellular and molecular basis for these declines remain unknown.
Inflammation and Skeletal Muscle Regenerative Potential
Elevated inflammatory cytokines are a feature of age-related skeletal muscle decline. However, the specific effects of age-related cytokine elevations on resident stem cell maintenance are unclear. Furthermore, how cytokine elevations intersect with other age-related disturbances such as lower hormone levels to regulate resident stem cell fate requires interrogation.