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

Abstract

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.

Inter-Person Differences in Isometric Coactivations of Triceps Surae and Tibialis Anterior Decrease in Young, but Not in Older Adults After 14 Days of Bed Rest

“…Our study has several limitations. First, the number of investigated participants that underwent the 14-day bed rest protocol is relatively low, but is comparable to many other studies that compared young vs. older participants (Erim et al, 1999, 20 participants;Connelly et al, 1999, 12 participants;Vaillancourt et al, 2003, 30 participants;Kallio et al, 2012, 17 participants;Castronovo et al, 2018, 20 participants) as well as to other bed rest studies where the number of participants ranged from 6 to 16 (Di Girolamo et al, 2021). This is partially justified by the complexity and stress of the prolonged bed rest that needs to be carried out in a hospital setting with 24-h medical inspection and care.…”

“…Experimental bed rest is a gold standard ground-based model for studying the effects of microgravity, as well as interaction between aging and disuse (Di Girolamo et al, 2021). Post bed rest decreases of muscle mass and strength (Koren, 2015;Pišot et al, 2016;Rejc et al, 2018;Marusic et al, 2021), as well as performance and neural drive (Duchateau, 1995) were reported in the past, along with the damaged neuromuscular junctions and muscle denervation (Monti et al, 2021).…”

Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic

“…Experimental BR is one of the most appropriate methods to study the consequences of immobilization in a standardized and controlled environment (35). This approach has been recognized to be of potential clinical relevance for mimicking hospitalrelated physical inactivity since it allows differentiating the catabolic effects induced by a disease from those secondary to skeletal muscle disuse (35).…”

“…Experimental BR is one of the most appropriate methods to study the consequences of immobilization in a standardized and controlled environment (35). This approach has been recognized to be of potential clinical relevance for mimicking hospitalrelated physical inactivity since it allows differentiating the catabolic effects induced by a disease from those secondary to skeletal muscle disuse (35). The study of healthy volunteers in facilities that allow a controlled modification of the amount of oxygen in the air in both bed rest and/or ambulatory conditions can be considered an appropriate model to investigate the separate and the combined effect of hypoxia and muscle disuse (28,36,37).…”

Introduction to Neuromechanics, a New MDPI Open Access Section of Biomechanics

“…With advancements in technology from the molecular to the modeled system level, neuromechanics is strategically positioned to advance the diagnoses and prognoses of clinical conditions and analyze and increase sports performance. The Neuromechanics section will welcome submissions to report novel data on: • Force generation in fresh and fatigued states by skeletal muscle from the cellular to system level and its adaptation to treatments, supplemented by neurophysiological measurements in health and disease [12,13]; • Dynamic characterization of tendon properties and tracking the adaptation of tendons to interventions using high resolution imaging [14-18];…”