The Aging Muscle in Experimental Bed Rest: A Systematic Review and Meta-Analysis

Background: Maintaining skeletal muscle mass and function in aging is crucial for preserving the quality of life and health. An experimental bed rest (BR) protocol is a suitable model to explore muscle decline on aging during inactivity.Objective: The purpose of this systematic review and meta-analysis was, therefore, to carry out an up-to-date evaluation of bed rest, with a specific focus on the magnitude of effects on muscle mass, strength, power, and functional capacity changes as well as the mechanisms, molecules, and pathways involved in muscle decay.Design: This was a systematic review and meta-analysis study.Data sources: We used PubMed, Medline; Web of Science, Google Scholar, and the Cochrane library, all of which were searched prior to April 23, 2020. A manual search was performed to cover bed rest experimental protocols using the following key terms, either singly or in combination: “Elderly Bed rest,” “Older Bed rest,” “Old Bed rest,” “Aging Bed rest,” “Aging Bed rest,” “Bed-rest,” and “Bedrest”. Eligibility criteria for selecting studies: The inclusion criteria were divided into four sections: type of study, participants, interventions, and outcome measures. The primary outcome measures were: body mass index, fat mass, fat-free mass, leg lean mass, cross-sectional area, knee extension power, cytokine pattern, IGF signaling biomarkers, FOXO signaling biomarkers, mitochondrial modulation biomarkers, and muscle protein kinetics biomarkers.Results: A total of 25 studies were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. In total, 118 healthy elderly volunteers underwent 5-, 7-, 10-, or 14-days of BR and provided a brief sketch on the possible mechanisms involved. In the very early phase of BR, important changes occurred in the skeletal muscle, with significant loss of performance associated with a lesser grade reduction of the total body and muscle mass. Meta-analysis of the effect of bed rest on total body mass was determined to be small but statistically significant (ES = −0.45, 95% CI: −0.72 to −0.19, P < 0.001). Moderate, statistically significant effects were observed for total lean body mass (ES = −0.67, 95% CI: −0.95 to −0.40, P < 0.001) after bed rest intervention. Overall, total lean body mass was decreased by 1.5 kg, while there was no relationship between bed rest duration and outcomes (Z = 0.423, p = 672). The meta-analyzed effect showed that bed rest produced large, statistically significant, effects (ES = −1.06, 95% CI: −1.37 to −0.75, P < 0.001) in terms of the knee extension power. Knee extension power was decreased by 14.65 N/s. In contrast, to other measures, meta-regression showed a significant relationship between bed rest duration and knee extension power (Z = 4.219, p < 0.001). Moderate, statistically significant, effects were observed after bed rest intervention for leg muscle mass in both old (ES = −0.68, 95% CI: −0.96 to −0.40, P < 0.001) and young (ES = −0.51, 95% CI: −0.80 to −0.22, P < 0.001) adults. However, the magnitude of change was higher in older (MD = −0.86 kg) compared to younger (MD = −0.24 kg) adults.Conclusion: Experimental BR is a suitable model to explore the detrimental effects of inactivity in young adults, old adults, and hospitalized people. Changes in muscle mass and function are the two most investigated variables, and they allow for a consistent trend in the BR-induced changes. Mechanisms underlying the greater loss of muscle mass and function in aging, following inactivity, need to be thoroughly investigated.

Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study

Background: Central obesity is associated with increased risk of cardiometabolic disease. Weight loss reduces lean muscle mass, potentially impacting resting energy expenditure and/or physical functioning. This analysis of the STEP 1 trial evaluated the impact of subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, on body composition in adults with overweight/obesity using dual energy X-ray absorptiometry (DEXA). Methods: In STEP 1, 1961 adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without diabetes, were randomized to s.c. semaglutide 2.4 mg once-weekly or matched placebo (2:1) for 68 weeks, plus lifestyle intervention. Participants with BMI ≤40 kg/m2 from 9 sites were eligible for the substudy. Total fat mass, total lean body mass and regional visceral fat mass were measured using DEXA at screening and week 68; visceral fat mass was calculated in the L4 region (both males/females), android region (males), or gynoid region (females), depending on site scanner methodology. Proportions of total fat and lean body mass are shown relative to total body mass; proportion of visceral fat mass is expressed relative to region assessed. Results: This analysis included 140 participants (semaglutide n=95; placebo n=45) (mean weight 98.4 kg, BMI 34.8 kg/m2; 76% female). Baseline body composition was similar in those receiving semaglutide and placebo (total fat mass proportion: 43.4% vs 44.6%; regional visceral fat mass proportion: 33.8% vs 36.3%; total lean body mass proportion: 53.9% vs 52.7%; respectively). Percentage change in body weight from baseline to week 68 was -15.0% with semaglutide vs -3.6% with placebo. This resulted in reductions from baseline with semaglutide in total fat mass (-19.3%) and regional visceral fat mass (-27.4%), leading to 3.5%-point and 2.0%-point reductions in the proportions of total fat mass and visceral fat mass, respectively. Total lean body mass decreased from baseline (-9.7%); however, the proportion relative to total body mass increased by 3.0%-points. An increasing improvement in lean body mass:fat mass ratio was seen with semaglutide with increasing weight loss from baseline to week 68 (continuous data). Overall, the ratio increased from baseline (1.34 [95% CI: 1.22, 1.47]) to week 68 by 0.23 [0.14, 0.32], with greater improvement in those with ≥15% weight loss (n=44; 0.41 [0.28, 0.53]) vs <15% weight loss (n=39; 0.03 [-0.05, 0.12]) (observed, dichotomized data; no imputation for missing data). There were no major changes in body composition with placebo from baseline to week 68. Conclusion: In adults with overweight/obesity, semaglutide 2.4 mg was associated with reduced total fat mass and regional visceral fat mass, and an increased proportion of lean body mass. Greater weight loss was associated with greater improvement in body composition (lean body mass:fat mass ratio).

The Relationship of Lean Body Mass With Aging to the Development of Diabetes

Context Older adults have the greatest burden of diabetes; however, the contribution of age-related muscle loss to its development remains unclear. Objective We assessed the relationship of lean body mass with aging to incident diabetes in community-dwelling adults. Design and Setting We studied participants in the Baltimore Longitudinal Study of Aging with median follow-up of 7 years (range 1-16). Cox proportional hazard models with age as the time scale were used. Time-dependent lean body mass measures were updated at each follow-up visit available. Participants Participants included 871 men and 984 women without diabetes who had ≥ 1 assessment of body composition using dual x-ray absorptiometry. Main Outcomes Incident diabetes, defined as self-reported history and use of glucose-lowering medications; or fasting plasma glucose ≥ 126 mg/dL and 2-hour oral glucose tolerance test glucose ≥ 200 mg/dL either at the same visit or 2 consecutive visits. Results The baseline mean [standard deviation] age was 58.9 [17.3] years. Men and women with a higher percentage of total lean body mass had lower fasting and 2-hour glucose levels, and less prediabetes (all P < 0.01). Among men, comparing highest versus lowest quartiles, percentage of total lean body mass (hazard ratio [HR], 0.46; 95% confidence interval, 0.22-0.97), percentage leg lean mass (HR, 0.38; 0.15-0.96), and lean-to-fat mass ratio (HR, 0.39; 0.17-0.89) were inversely associated with incident diabetes after accounting for race and attenuated after adjustment for height and weight. Conversely, absolute total lean body mass was positively associated with incident diabetes among women, with similar trends in men. No associations were observed with muscle strength or quality. Conclusions Relatively lower lean body mass with aging is associated with incident diabetes in men and partially related to anthropometrics, but not so in women.

Ways to optimize the assessment of lean body mass in hemodialysis patients

The aim. To conduct a comparative analysis of the effectiveness of methods for assessing lean body mass in haemodialysis patients. Patients and methods. A total of 317 patients receiving treatment with programmatic bicarbonate haemodialysis in 9 haemodialysis centers in 5 regions of the European part of the Russian Federation were examined for 8.2 ± 5.1 years, among them 171 women and 146 men, the average age was 57.1 ± 11.3 years. Dual-energy X-ray absorptiometry and bioimpedancemetry were used to assess lean body mass. Results. The results of determining the total lean body mass obtained from the results of dual-energy X-ray absorptiometry and bioimpedancemetry were compared using the Bland-Altman method. The correlation coefficient between the indicators was r = 0.994, p < 0.0001, delta (M ± σ) was –0.48 ± 0.91 kg, CI 95% (–0.71)–(–0.26) kg. Conclusion. Dual-energy X-ray absorptiometry has no significant advantages compared with bioimpedancemetry when evaluating lean body mass in haemodialysis patients.

1H-NMR analysis of the human urinary metabolome in response to an 18-month multi-component exercise program and calcium–vitamin-D3supplementation in older men

The musculoskeletal benefits of calcium and vitamin-D3supplementation and exercise have been extensively studied, but the effect on metabolism remains contentious. Urine samples were analyzed by1H-NMR spectroscopy from participants recruited for an 18-month, randomized controlled trial of a multi-component exercise program and calcium and vitamin-D3fortified milk consumption. It was shown previously that no increase in musculoskeletal composition was observed for participants assigned to the calcium and vitamin-D3intervention, but exercise resulted in increased bone mineral density, total lean body mass, and muscle strength. Retrospective metabolomics analysis of urine samples from patients involved in this study revealed no distinct changes in the urinary metabolome in response to the calcium and vitamin-D3intervention, but significant changes followed the exercise intervention, notably a reduction in creatinine and an increase in choline, guanidinoacetate, and hypoxanthine (p < 0.001, fold change > 1.5). These metabolites are intrinsically involved in anaerobic ATP synthesis, intracellular buffering, and methyl-balance regulation. The exercise intervention had a marked effect on the urine metabolome and markers of muscle turnover but none of these metabolites were obvious markers of bone turnover. Measurement of specific urinary exercise biomarkers may provide a basis for monitoring performance and metabolic response to exercise regimes.