Genetic Control of Heart Function and Aging in Drosophila☆

Abstract 

The Drosophila heart has proven itself to be an excellent model for human cardiac development and recent investigations suggest that it may serve as a model for human heart function as well. Just as tinman-related genes underlie cardiac development in all organisms with a heart, the functional properties of mature hearts also appear to be conserved in the animal kingdom. Ion channels, such as those encoded by the potassium channel genes KCNQ and HERG, contribute to normal heart function in humans and flies, and when malfunctioning, cause cardiomyopathies or arrhythmias in remarkably similar ways in both species. Moreover, the K_ATP channel encoded by dSUR protects the heart against hypoxia/ischemia in flies and mammals, and this protection seems to be reduced with age. Indeed, aging appears to affect heart function and performance in flies in ways that are reminiscent of the decline in human heart function with age, and this likely includes a cardiac autonomous function for the insulin-signaling pathway. The potential for discovery of new genes, such as the two-pore ORK1 K⁺ channel that affects heart rate in flies, makes Drosophila an attractive heart model for genome-wide screens and for complex genetic manipulations needed to elucidate the mechanisms contributing to cardiac malfunction. Insights gained from the fly heart may prove to be instrumental in unraveling the mysteries of the human heart in health and disease.