Such sarcomere lengths put high strain on titin (Figure 1A, right panel), providing a potent trigger for mechanosensing and subsequent hypertrophy signaling. (A) Schematic of how UDD affects sarcomere length in the denervated costal (left panel) and how stretch extends titin for mechanosensing (right panel). A substantial part of the hypertrophy seen in mice encompasses longitudinal hypertrophy (C), lengthening of the muscle fibers by addition of serial sarcomeres (n=10–13). To study how titin compliance might affect the hypertrophy response in UDD, we performed UDD on Rbm20ΔRRM mice and Rbm20 KO rats. Thus, muscle stretch in the costal diaphragm is a potent trigger for longitudinal muscle hypertrophy, with titin being a primary sensor.