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. 2017 Apr 1;122(4):775-787.
doi: 10.1152/japplphysiol.00830.2016. Epub 2017 Jan 12.

Moderate-intensity resistance exercise alters skeletal muscle molecular and cellular structure and function in inactive older adults with knee osteoarthritis

Mark S Miller  1   2 , Damien M Callahan  3 , Timothy W Tourville  4   5 , James R Slauterbeck  4 , Anna Kaplan  3 , Brad R Fiske  3 , Patrick D Savage  3 , Philip A Ades  3 , Bruce D Beynnon  4 , Michael J Toth  3   1   4
Affiliations

Moderate-intensity resistance exercise alters skeletal muscle molecular and cellular structure and function in inactive older adults with knee osteoarthritis

Mark S Miller et al. J Appl Physiol (1985). .

Abstract

High-intensity resistance exercise (REX) training increases physical capacity, in part, by improving muscle cell size and function. Moderate-intensity REX, which is more feasible for many older adults with disease and/or disability, also increases physical function, but the mechanisms underlying such improvements are not understood. Therefore, we measured skeletal muscle structure and function from the molecular to the tissue level in response to 14 wk of moderate-intensity REX in physically inactive older adults with knee osteoarthritis (n = 17; 70 ± 1 yr). Although REX training increased quadriceps muscle cross-sectional area (CSA), average single-fiber CSA was unchanged because of reciprocal changes in myosin heavy chain (MHC) I and IIA fibers. Intermyofibrillar mitochondrial content increased with training because of increases in mitochondrial size in men, but not women, with no changes in subsarcolemmal mitochondria in either sex. REX increased whole muscle contractile performance similarly in men and women. In contrast, adaptations in single-muscle fiber force production per CSA (i.e., tension) and contractile velocity varied between men and women in a fiber type-dependent manner, with adaptations being explained at the molecular level by differential changes in myosin-actin cross-bridge kinetics and mechanics and single-fiber MHC protein expression. Our results are notable compared with studies of high-intensity REX because they show that the effects of moderate-intensity REX in older adults on muscle fiber size/structure and myofilament function are absent or modest. Moreover, our data highlight unique sex-specific adaptations due to differential cellular and subcellular structural and functional changes.NEW & NOTEWORTHY Moderate-intensity resistance training causes sex-specific adaptations in skeletal muscle structure and function at the cellular and molecular levels in inactive older adult men and women with knee osteoarthritis. However, these responses were minimal compared with high-intensity resistance training. Thus adjuncts to moderate-intensity training need to be developed to correct underlying cellular and molecular structural and functional deficits that are at the root of impaired physical function in this mobility-limited population.

Keywords: mitochondria; myofilament; sex differences; training.

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Figures

Fig. 1.
Fig. 1.
Training-induced adaptations in quadriceps (A and B) and single-fiber (C–F) cross-sectional area (CSA). IHC, immunohistochemistry. Data represent means ± SE *P ≤ 0.05, **P < 0.01 for training effect. Note that there were no training × sex interaction effects for any comparisons.
Fig. 2.
Fig. 2.
A–D: representative images showing electron micrographs (A and B) and highlighted mitochondria only (C and D) for an older male volunteer pre- and posttraining. E–J: training-induced adaptations in intermyofibrillar mitochondria (IMF) in the entire cohort (E, G, and I) and in men and women separately (F, H, and J), as assessed by electron microscopy. Data represent means ± SE. Lines extending across all sexes and times reflect training × sex interaction effects, while lines extending across pre- and posttraining assessments within each sex denote differences from post hoc, pairwise comparisons. *P < 0.05, **P < 0.01, +trends (P = 0.07 and 0.08 for IMF count and IMF area, respectively) for training or training × sex interaction effects. Note that differences in fiber CSA between chemically skinned single-muscle fiber CSA and IHC CSA are related to the swelling that occurs upon chemical skinning, as we have demonstrated previously (10).
Fig. 3.
Fig. 3.
Training-induced adaptations in single MHC I fiber maximal Ca2+-activated tension (Tmax; A and B), tension at maximum power production (Topt, C), and power-tension relationships (D). All measurements were conducted at 15°C, except for Tmax at 25°C (B). Tension = force/CSA. Data represent means ± SE. *P ≤ 0.05, **P < 0.01 for training × sex effect (bar across all groups/time points) or post hoc comparison for training effect within each sex (bar across each sex separately).
Fig. 4.
Fig. 4.
Training-induced adaptations in cross-bridge mechanics and kinetics in single MHC I fibers (A–F) and the relationship between training-induced changes in the number of strongly bound cross bridges (mechanics variable B in C) and ton (G). All measurements were conducted at 25°C. Details of the physiological interpretation of each parameter are provided in Molecular-Level Contractile Function Measurements. Data represent means ± SE. *P < 0.05 for training × sex effect (bar across all groups/time points) or post hoc comparison for training effect within each sex (bar across each sex separately); +P = 0.06 for training × sex effect.
Fig. 5.
Fig. 5.
Training-induced adaptations in single-MHC IIA fiber Tmax at 25°C (A), A-elastic (B), and the relationship between changes in Tmax and A-elastic (C). Tension = force/CSA. Data represent means ± SE. *P ≤ 0.05 for training × sex effect; +P = 0.07 for training effect.
Fig. 6.
Fig. 6.
Training-induced adaptations in MHC IIAX fiber velocity at maximum power output (Vopt; A), power-velocity relationships (B), the fractional expression of MHC IIX in MHC IIAX fibers pooled from cellular and molecular functional assessments (C), myosin attachment time (ton; D), and the relationship between ton and the fractional expression of MHC IIX in single MHC IIAX fibers assessed for molecular function (E). Measurements were conducted at 15°C for A and B and at 25°C for D and E. Data represent means ± SE. *P ≤ 0.05 for training × sex effect (bar across all groups/time points) or training effect (across each sex separately); **P < 0.01 for training × sex effect; +P = 0.06 for training effect.
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