Abstract: Provided herein are in vitro and in vivo methods of inducing cardiomyocyte proliferation by contacting cardiomyocytes with or administering to a subject an effective amount of an agent capable of activating sterol biosynthesis, such as mevalonate biosynthesis. Methods and compositions for regenerating a cardiac tissue in a subject that include administering thereto a therapeutically effective amount of an agent capable of activating sterol biosynthesis in a cardiomyocyte are also provided herein.