Age-related differences in the loss and recovery of serial sarcomere number following disuse atrophy in rats

Abstract Background Older adults exhibit a slower recovery of muscle mass following disuse atrophy than young adults. At a smaller scale, muscle fibre cross-sectional area (i.e., sarcomeres in parallel) exhibits this same pattern. Less is known, however, about age-related differences in the recovery of muscle fibre length, driven by increases in serial sarcomere number (SSN), following disuse. The purpose of this study was to investigate age-related differences in SSN adaptations and muscle mechanical function during and following muscle immobilization. We hypothesized that old rats would experience a similar magnitude of SSN loss during immobilization, however, take longer to recover SSN than young following cast removal, which would limit the recovery of muscle mechanical function. Methods We casted the plantar flexors of young (8 months) and old (32 months) male rats in a shortened position for 2 weeks, and assessed recovery during 4 weeks of voluntary ambulation. Following sacrifice, legs were fixed in formalin for measurement of soleus wet weight and SSN with the un-casted soleus acting as a control. Ultrasonographic measurements of pennation angle (PA) and muscle thickness (MT) were also conducted weekly. In-vivo active and passive torque-angle relationships were constructed pre-cast, post-cast, and following 4 weeks of recovery. Results From pre- to post-cast, young and old rats experienced similar decreases in SSN (–20%, P <0.001), muscle wet weight (–25%, P <0.001), MT (–30%), PA (–15%, P <0.001), and maximum isometric torque (–40%, P <0.001), but there was a greater increase in passive torque in old (+180%, P <0.001) compared to young rats (+68%, P =0.006). Following cast removal, young exhibited quicker recovery of SSN, PA, and MT than old, but SSN recovered sooner than PA and MT in both young and old. Muscle wet weight recovered 90% and active torque fully recovered in young rats, whereas in old these remained unrecovered at 75% and 72%, respectively. Conclusions This study showed that old rats retain a better ability to recover longitudinal compared to parallel muscle morphology following cast removal, making SSN a highly adaptable, appealing mechanism for restoration of functional capacity following disuse in elderly populations.