The Role of Ubiquitin-Proteasome System (UPS)-Associated Genes in the Preservation of Cardiac and Muscle Function in Drosophila melanogaster

One of the leading causes of death in the elderly is cardiovascular disease (CVD). Complications resulting from CVD kills an estimated 70% of people over 70 years old. Understanding key factors associated with age associated heart function decline remains a critical step in identifying targets for therapeutic interventions. Previous studies have implicated a decline in proteostasis in explaining declining cardiac function with age. Up until recently, researchers have focused heavily on autophagy as a major contributor to cardiac aging, but relatively little has been discerned about the role of the ubiquitin proteasome system (UPS) in aging heart cells. To gain greater understanding of this phenomenon the E2 ubiquitin ligase CG14739 was individually knocked down in cardiac and skeletal muscle. The expected outcome was a reduction in function due to loss of proteostasis. Reduced CG14739 in cardiac muscle resulted in an intensified age-associated decline in heart function, as indicated by decreased heart rate, diastolic function, and fractional shortening. In skeletal muscle, the reduction of CG14739 resulted in declining flight performance. Ideally, overexpressing UPS candidates will ameliorate age-associated cardiac function decline. Future work will test this hypothesis