The present invention provides a method of treating or preventing cardiac disorders in a subject in need thereof by inhibiting the expression or function of both miR-499 and miR-208 in the heart cells of the subject. In particular, specific protocols for administering inhibitors of the two miRNAs that achieve efficient, long-term suppression are disclosed. In addition, the invention provides a method for treating or preventing musculoskeletal disorders in a subject in need thereof by increasing the expression or activity of both miR-208 and miR-499 in skeletal muscle cells of the subject.