Colleen S. Deane

Horizontal bed rest (HBR) and head‐down tilt (HDT) are models of physical inactivity. In this systematic review and meta‐analysis, we aimed to quantify changes in cardiometabolic outcomes during HBR and HDT in healthy adults. Following the PRISMA guidelines, we searched PubMed, Scopus, Web of Science and Cochrane Library until 1 October 2025. Included studies recruited healthy adults (≥18 years of age) undergoing ≥2 days of HBR or HDT. A meta‐analysis with mean differences (MD) and 95% confidence intervals (CI), using random‐effects modelling was conducted. Forty‐four studies were included. HBR (≤14 days) reduced fasting glucose (MD, −0.15 mmol/L, P = 0.00033). HBR (≤14 days) and HDT (≤60 days) increased insulin (HBR: MD, 7.07 pmol/L; HDT: MD, 9.65 pmol/L; P  < 0.0001). The homeostatic model assessment for insulin resistance was increased under both models (HBR ≤30 days: MD, 0.10, P = 0.0004; HDT ≤60 days: MD, 0.24, P  < 0.0001). HDT lowered total cholesterol (MD: −13.89 mg/dL, P = 0.000467); HBR raised triglycerides (MD, 18.96 mg/dL, P  < 0.0001), and high‐density lipoprotein cholesterol was decreased in both models (HBR ≤14 days: MD, −4.53 mg/dL, P = 0.000608; HDT ≤60 days: MD, −6.89; P  < 0.0001). C‐Reactive protein was elevated in HBR (MD, 1.57; P  < 0.0001), and tumour necrosis factor alpha was elevated in both (HBR ≤14 days: MD, 1.33, P  < 0.0001; HDT ≤21 days: MD, 0.40; P = 0.00643). In conclusion, HBR and HDT induce model‐ and duration‐specific changes in glucose metabolism and lipid profiles. Interventions that could mitigate these effects may be warranted.

Background: Nutritional interventions to mitigate age/disease-related skeletal muscle attrition are much needed given the growing older population. Beta-hydroxy beta-methylbutyrate (HMB), an endogenous metabolite of the essential amino acid leucine, has anabolic properties in skeletal muscle: acutely stimulating muscle protein synthesis and attenuating muscle protein breakdown. While the role of supplemental HMB on muscle protein turnover is established, mechanistic effects on the muscle transcriptome have not been examined. Methods: Total RNA was extracted from m. vastus lateralis muscle biopsies of young males (n = 14) before and ~2.5 h after oral consumption of ~3 g HMB. Global changes in the muscle transcriptome were assessed via RNA sequencing, and differential expression in genes between fasted and ‘fed’ (HMB) conditions was determined. To identify the functional biology of differentially expressed genes, gene set enrichment and active subnetwork-orientated enrichment analyses was performed. Results: Of 15,982 genes detected, 468 were significantly upregulated and 326 were significantly downregulated in response to HMB. These genes were found to be associated with molecular pathways regulating muscle protein turnover, most notably, JAK-STAT signalling (e.g., STAM), circadian rhythm (e.g., NR1D1, NR1D2, PER2, PER3), TNFα signalling (e.g., TNFRSF1A, CCL2, CXCL2), and protein synthesis (e.g., POLR1A, POLR2A, POLR3A, PIK3RR, SGK1). HMB also regulated the expression of AA transporters, evoking a robust increase in SLC36A1 (PAT1) and SLC7A5 (LAT1). Conclusions: HMB evokes transcriptional events important in the homeostasis of muscle, supporting a role in proteostasis and one akin to protein intake, i.e., upregulation of AA transporters. Future work should further define HMB’s transcriptomic/proteomic effects in ageing/disease and synergy with exercise.

Purpose of review: To critically review recent findings related to the effects of omega-3 fatty acid supplementation on skeletal muscle, with a particular focus on skeletal muscle protein turnover and mitochondrial function. Recent findings: Evidence indicates that omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may support skeletal muscle health by influencing muscle protein synthesis (MPS), mitochondrial function, and redox balance. However, recent meta-analyses reveal inconsistent effects of omega-3 fatty acid supplementation on basal and stimulus-induced MPS, likely due to methodological variability. Omega-3 fatty acid supplementation is seemingly more beneficial in clinical cohorts and preclinical data suggests omega-3s may reduce oxidative stress. Summary: Omega-3 fatty acid supplementation is a promising nutritional strategy for supporting skeletal muscle health, via the modulation of MPS and mitochondrial function. However, large-scale trials in a variety of healthy and clinical populations using sustainable sources of omega-3 fatty acids are required before a consensus on efficacy can be made.

Spaceflight and partial-gravity environments impose profound challenges to the human musculoskeletal system, driving rapid muscle atrophy, progressive bone loss, and tendon maladaptation. At the molecular level, unloading suppresses anabolic signaling, enhances proteolysis, and induces mitochondrial stress, whereas bone and tendon exhibit reduced extracellular matrix turnover and impaired mechanotransduction. Recent space-omics and cross-species studies, including rodent and Caenorhabditis elegans models, reveal that these catabolic responses are evolutionarily conserved and involve systemic pathways mediated by myokines, osteokines, and tendon-derived signals. Current countermeasure strategies primarily consist of structured exercise regimens with limited pharmacologic support. Although these strategies mitigate some loss, they fail to fully preserve musculoskeletal integrity, particularly tendon properties and microarchitectural bone quality. Key gaps remain in the development of tendon-specific interventions, integrated pharmacologic and exercise regimens, nutrition and dietary protocols, and methods for partial-gravity adaptation and safe re-entry. Leveraging real-time monitoring, individualized exercise programs, and systemic biomarker discovery through space omics presents major opportunities for next-generation, personalized countermeasures. This mini-review synthesizes current knowledge of musculoskeletal responses with a particular focus on tendon maladaptation and interorgan cross talk to spaceflight and partial gravity, highlights countermeasure efficacy and limitations, and identifies critical gaps that must be addressed to ensure astronaut health and performance during future missions. Insights from these studies also provide translational relevance for disuse atrophy, osteoporosis, and tendon injuries on Earth.

Muscle disuse leads to muscle atrophy and a decrease in muscle function that is primarily driven by reduced muscle protein synthesis (MPS). The aim of this systematic review and meta‐analysis was to examine the effect of different models of muscle disuse on rates of MPS. A literature search was conducted in PubMed, Web of Science, Scopus and Cochrane Library. Eligible randomized and non‐randomized controlled trials compared the effect of bed rest (BR), unilateral lower limb immobilization (ULLI), and 6° head‐down tilt (HDT) on pre–post muscle disuse changes in MPS in adults. Using the random and fixed effects inverse‐variance model, we calculated the mean difference (MD) in the effect of BR on mixed MPS and ULLI on myofibrillar MPS (MyoPS) (both expressed as fractional synthetic rate,%/h). The effect of HDT on MPS was examined through a narrative synthesis of data. A total of 16 studies were included in the systematic review and 13 in the meta‐analysis. A significant reduction in mixed MPS was observed after BR ( k = 4; MD: −0.017%/h, 95% CI: −0.023 to −0.011, I ² = 24%, P < 0.01) and a significant reduction in MyoPS was observed after ULLI ( k = 9; MD: −0.015%/h, 95% CI: −0.021 to −0.008, I ² = 94%, P < 0.01). HDT led to reductions in both mixed MPS and MyoPS. A comparable reduction in mixed MPS and MyoPS was observed between different models of muscle disuse.