Novel individualized power training protocol preserves physical function in adult and older mice

Sarcopenia, the age-related loss of muscle mass and strength, contributes to frailty, functional decline, and reduced quality of life in older adults. Exercise is a recognized therapy for sarcopenia and muscle dysfunction, though not a cure. Muscle power declines at an increased rate compared to force, and force output declines earlier than mass. Thus, there is a need for research of exercise focusing on improving power output and functionality in older adults. Our primary purpose was proof-of-concept that a novel individualized power exercise modality would induce positive adaptations in adult mice, before the exercise program was applied to an aged cohort. We hypothesized that after following our protocol, both adult and older mice would show improved function, though there would be evidence of anabolic resistance in the older mice. Male C57BL/6 mice (12 months of age at study conclusion) were randomized into control (n = 9) and exercise (n = 6) groups. The trained group used progressive resistance (with a weighted harness) and intensity (~ 4-10 rpm) on a custom motorized running wheel. The mice trained similarly to a human workout regimen (4-5 sets/session, 3 sessions/week, for 12 weeks). We determined significant (p < 0.05) positive adaptations post-intervention, including: neuromuscular function (rotarod), strength/endurance (inverted cling grip test), training physiology (force/power output per session), muscle size (soleus mass), and power/velocity of contraction (in vitro physiology). Secondly, we trained a cohort of older male mice (28 months old at conclusion): control (n = 12) and exercised (n = 8). While the older exercised mice did preserve function and gain benefits, they also demonstrated evidence of anabolic resistance.F31 AG044108 - NIA NIH HHS; R01 AG017768 - NIA NIH HHS; TL1 TR001440 - Institute for Translational Sciences, University of Texas Medical BranchAccepted manuscrip

Increasing myosin light chain 3f (MLC3f) protects against a decline in contractile velocity

Disuse induces adaptations in skeletal muscle, which lead to muscle deterioration. Hindlimb-unloading (HU) is a well-established model to investigate cellular mechanisms responsible for disuse-induced skeletal muscle dysfunction. In myosin heavy chain (MHC) type IIB fibers HU induces a reduction in contraction speed (Vo) and a reduction in the relative myosin light chain 3f (MLC3f) protein content compared with myosin light chain 1f (MLC1f) protein. This study tested the hypothesis that increasing the relative MLC3f protein content via rAd-MLC3f vector delivery would attenuate the HU-induced decline in Vo in single MHC type IIB fibers. Fischer-344 rats were randomly assigned to one of three groups: control, HU for 7 days, and HU for 7 days plus rAd-MLC3f. The semimembranosus muscles were injected with rAd-MLC3f (3.75 x 1011-5 x 1011 ifu/ml) at four days after the initiation of HU. In single MHC type IIB fibers the relative MLC3f content decreased by 25% (12.00±0.60% to 9.06±0.66%) and Vo was reduced by 29% (3.22±0.14fl/s vs. 2.27±0.08fl/s) with HU compared to the control group. The rAd-MLC3f injection resulted in an increase in the relative MLC3f content (12.26±1.19%) and a concomitant increase in Vo (2.90±0.15fl/s) of MHC type IIB fibers. A positive relationship was observed between the percent of MLC3f content and Vo. Maximal isometric force and specific tension were reduced with HU by 49% (741.45±44.24μN to 379.09±23.77μN) and 33% (97.58±4.25kN/m2 to 65.05±2.71kN/m2), respectively compared to the control group. The rAd-MLC3f injection did not change the HU-induced decline in force or specific tension. Collectively, these results indicate that rAd-MLC3f injection rescues hindlimb unloading-induced decline in Vo in MHC type IIB single muscle fibers.Published versio