Neuromuscular Electrical Stimulation Combined with Protein Ingestion Preserves Thigh Muscle Mass But Not Muscle Function in Healthy Older Adults During 5 Days of Bed Rest

Abstract

Short-term bed rest in older adults is characterized by significant loss in leg lean mass and strength posing significant health consequences. The purpose of this study was to determine in healthy older adults if the daily combination of neuromuscular electrical stimulation and protein supplementation (NMES+PRO) would protect muscle mass and function after 5 days of bed rest. Twenty healthy older adults (∼70 years) were subjected to 5 days of continuous bed rest and were randomized into one of two groups: NMES+PRO (n = 10) or control (CON) (n = 10). The NMES+PRO group received bilateral NMES to quadriceps (40 minutes/session, 3 × /day; morning, afternoon, and evening) followed by an interventional protein supplement (17 g). The CON group received an isocaloric equivalent beverage. Before and after bed rest, vastus lateralis biopsies occurred before and after acute essential amino acid (EAA) ingestion for purposes of acutely stimulating mechanistic target of rapamycin (mTORC1) signaling, a major regulator of muscle protein synthesis, in response to bed rest and NMES+PRO. Baseline (pre and post bed rest) muscle samples were also used to assess myofiber characteristics and gene expression of muscle atrophy markers. Thigh lean mass and muscle function were measured before and after bed rest. Five days of bed rest reduced thigh lean mass, muscle function, myofiber cross-sectional area, satellite cell content, blunted EAA-induced mTORC1 signaling, and increased myostatin and MAFbx mRNA expression. Interestingly, NMES+PRO during bed rest maintained thigh lean mass, but not muscle function. Thigh muscle preservation during bed rest with NMES+PRO may partly be explained by attenuation of myostatin and MAFbx mRNA expression rather than restoration of nutrient-induced mTORC1 signaling. We conclude that the combination of NMES and protein supplementation thrice a day may be an effective therapeutic tool to use to preserve thigh muscle mass during periods of short-term hospitalization in older adults. However this combined intervention was not effective to prevent the loss in muscle function.

Keywords: NMES; aging; atrophy; disuse; leucine; mTORC1.

FIG. 1.

Experimental design. Participants underwent 5 days of bed rest and were randomized into a CON or NMES+PRO group. The NMES+PRO treatment group was given NMES and a protein supplement thrice a day (morning, afternoon, and evening) for a total of 12 sessions. The first NMES+PRO treatment session was provided immediately after the first acute nutrient study experiment. Muscle strength and power were measured before and after bed rest. Tissue composition using DXA scan was determined before and at day 4 of bed rest. CON, control; DXA, dual energy X-ray absorptiometry; NMES+PRO, neuromuscular electrical stimulation and protein supplementation.

FIG. 2.

NMES+PRO effects on thigh lean mass. Figure denotes the change in thigh lean muscle after 5 days of bed rest in the CON (n = 10) and NMES+PRO (n = 10) groups and are reported as mean ± SEM. Data are reported as the percent change in thigh lean mass from pre-bed rest levels. *Different from PreBR (p < 0.05). ^#Different from NMES+PRO (p < 0.05). BR, bed rest.

FIG. 3.

NMES+PRO effects on leg muscle function. Figure denotes the change in (A) leg isometric strength and (B) leg power after 5 days of bed rest in the CON (n = 10) and NMES+PRO (n = 10) groups and are reported as mean ± SEM. Data are reported as the percent change from pre-bed rest levels. *Different from PreBR (p < 0.05).

FIG. 4.

NMES+PRO effects on muscle mTORC1 signaling. Figure denotes the skeletal muscle protein expression for (A) S6K1 (Thr389), (B) rpS6 (Ser240/244), (C) 4EBP1 (Thr37/46), (D) REDD1, and (E) REDD2 before and after 5 days of bed rest in the CON (n = 10) and NMES+PRO (n = 10) groups. Participants consumed a bolus of EAA in the fasted state, and protein expression for mTORC1 signaling proteins was determined at 0 (Basal), 45, and 90 minutes after EAA ingestion. Data (mean ± SEM) are reported as fold change from basal. Phosphorylated targets were normalized to total protein levels of the target protein. REDD1 and REDD2 were normalized to GAPDH. EAA, essential amino acid; mTORC1, mechanistic target of rapamycin.

FIG. 5.

NMES+PRO effects on muscle gene expression. Figure denotes the skeletal muscle mRNA expression for (A) MURF-1, (B) MAFbx, (C) myostatin, and (D) MyoD before and after 5 days of bed rest in the CON (n = 10) and NMES+PRO (n = 9) groups and are reported as mean ± SEM. There was insufficient muscle tissue for RNA isolation for one of the NMES+PRO participants; therefore data are only reported in n = 9 for this group. *Different from PreBR (p < 0.05). ^#Different from NMES+PRO (p < 0.05).