Two Weeks of Reduced Steps Disrupts Integrated Rates of Muscle Protein Synthesis and Glycemic Control in Healthy Older Adults

Abstract

Transient periods of physical inactivity can result in losses of skeletal muscle mass and reductions in insulin sensitivity. These metabolic impairments may not be fully recovered, particularly in older individuals.1 We aimed to examine the impact of two weeks of reduced steps followed by two weeks of recovery, on lean body mass (LBM), integrated rates of myofibrillar protein synthesis (MPS), single fiber cross‐sectional area (fCSA), and indices of glycemic control (HOMA‐IR and MATSUDA) in response to an oral glucose tolerance test. We also examined changes in oxidative phosphorylation protein complex content, phosphorylation of other related signaling molecules, and concentration of circulating inflammatory markers. Twenty‐two healthy older adults (12 men, 10 women, 69±4yr [all data mean±SD]) underwent 7d of monitored normal activity at baseline (BL) before reducing their daily step‐count from 7362±3294 to 990±97 steps.d−1 for 14d (SR). Habitual step count was then recovered for a period of 14d (RC). Integrated rates of muscle protein synthesis (MPS) were reduced from BL at SR (BL 1.51±0.07 to SR 1.33±0.05 %.d−1, p<0.05) and were not restored at RC (1.34±0.14 %.d−1). Women displayed significantly greater rates of integrated MPS at BL compared to men (1.56±0.06 vs. 1.47±0.04 %.d−1, p<0.05). HOMA‐IR increased from BL to SR (2.6±0.4 to 3.8±0.9, p<0.05) and MATSUDA decreased (3.9±0.7 to 2.9±0.4, p<0.05), neither recovered at RC. Glucose AUC was significantly elevated from BL at SR (368±137 to 442±142, p<0.05) and was not fully recovered from SR at RC (393±15). Insulin AUC increased from BL to SR (3372±889 to 3972±1008, p<0.05) and was still elevated at RC (3865±716). Circulating plasma TNF‐a was significantly increased from BL at SR (11.78±2.84 to 15.41±4.64 pg.mL−1, p<0.05) and was still elevated above BL at RC (14.28±3.76 pg.mL−1). Plasma IL‐6 concentration was also significantly increased from BL at SR (8.33±3.06 to 10.84± 4.35 pg.mL−1, p<0.05) and remained elevated at RC (9.99±4.37 pg.mL−1). There was no detectable impact of step reduction on LBM, fCSA, fiber type distribution, or the content of oxidative phosphorylation protein complexes at any time point. Additionally, step reduction failed to impact the phosphorylation status of ACCSer212, AktSer473, mTORSer2448, Ulk1Ser757, and Ulk1Ser55 at BL, SR, and RC. These data demonstrate that two weeks of step reduction leads to lowered rates of MPS that are accompanied by appearance of a diabetic phenotype, and markers of an inflammatory state, which are not recovered on return to a normal daily step count in healthy older adults. Ultimately, proactive interventions such as exercise or pharmaceuticals may be required to reverse decrements in metabolic health with transient periods of physical inactivity in this population.Support or Funding InformationSupported by the Canadian Diabetes Association