With age, cardiac performance declines progressively and the risk of heart disease, a primary cause of mortality, rises dramatically. As the elderly population continues to increase, it is critical to gain a better understanding of the genetic influences and modulatory factors that impact cardiac aging. As for the human heart, Drosophila heart function also deteriorates with age. Here,In order to better utilize the Drosophila heart model for genetic mechanism studies of cardiac aging, and supply more reliable evidences for molecular-guided diagnostics and therapeutics of age-related heart disease, we sum up the characteristics of cardiac aging of Drosophila in comparative medicine and review genetic factors contributing to cardiac aging, including genes involved in ion exchange, nutrient sensing, and contractile function. These achievements will provide a theoretical basis for molecular guided diagnostics and targeted drug therapied for cardiac aging related diseases, and promote the rapid development of precision medicine of cardiovascular disease.