Mechano‐therapy using high loads enhances regrowth of skeletal muscle in young, but induces muscle damage in old rats.

Abstract

IntroductionOlder adults have an impaired ability to recover from skeletal muscle atrophy compared to young, predisposing them to loss of independence and poor quality of life. We have previously shown that mechano‐therapy in the form of cyclic, compressive loading (CCL) enhances regrowth of atrophied skeletal muscle in young adult rats, but not in old. Our preliminary data show that passive, transverse stiffness of muscles from old rats is elevated compared to young, potentially blunting the mechanical stimulus and subsequent growth response. In the current study, we hypothesized that an increased CCL load proportional to the higher tissue stiffness in old rats would enhance skeletal muscle regrowth when compared to atrophied muscles of old rats subjected to a lower load of CCL or ambulation alone.MethodsYoung (10 months; N = 6) and old (30 months; N = 6) adult male F344/Brown Norway rats underwent 14 days of hind limb suspension before being randomly assigned to one of the following: reloading for 7 days without CCL (RE); reloading with 4.5 N CCL (RE + CCL, 4.5 N); or reloading with 7.6 N CCL (RE + CCL, 7.6 N). Starting on day 0, four bouts of CCL were administered to the right gastrocnemius using a custom designed device capable of applying a precise load, with 48 hrs between bouts. Gastrocnemius muscle sections were analyzed for muscle fiber cross‐sectional area (CSA), satellite cell abundance (Pax7+/fiber), embryonic myosin heavy chain expression (eMyHC+/fiber) and centro‐nucleation using immunohistochemistry.ResultsMuscle fiber CSA was load dependent in young adult rats, but had no effect at either load in old rats. When compared to muscles from RE rats, 4.5 N CCL had no effect on satellite cell abundance regardless of age; however, satellite cell abundance was higher in both young and old adult muscle after 7.6 N CCL compared to RE with old rats having 2‐fold higher levels compared to RE. Regardless of load, CCL was not associated with differences in eMyHC expression or centrally located nuclei in young adult rat muscle, while muscles receiving 7.6 N CCL in old rats had a higher number of centrally located nuclei and were ~16‐fold higher in eMyHC+ fibers compared to RE.ConclusionsThese results show that CCL induces a load dependent anabolic response in young adult animals during muscle mass recovery following disuse, but has no regrowth effect on muscles from old animals at either load. Furthermore, using a higher CCL load, scaled for elevated transverse stiffness in aged muscle, induces damage in muscle of old but not young rats.Support or Funding InformationThis research was supported by NIH grant RO1AT009268 and R21AG042699.