Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a ‘Combined Oral Stable Isotope Assessment of Muscle (COSIAM)’ approach

Cegielski, Jessica; Wilkinson, Daniel J.; Brook, Matthew S.; Boereboom, Catherine; Phillips, Bethan E.; Gladman, John F. R.; Smith, Kenneth; Atherton, Philip J.

Abstract

Optimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits the applicability of these approaches in certain populations (e.g. clinical, frail elderly). To concurrently quantify skeletal muscle mass and muscle protein turnover i.e. muscle protein synthesis (MPS) and muscle protein breakdown (MPB), in elderly human volunteers using stable-isotope labelled tracers i.e. Methyl-[D3]-creatine (D3-Cr), deuterium oxide (D2O), and Methyl-[D3]-3-methylhistidine (D3-3MH), to measure muscle mass, MPS and MPB, respectively. We recruited 10 older males (71 ± 4 y, BMI: 25 ± 4kg.m2, mean ± SD) into a 4-day study, with DXA and consumption of D2O and D3-Cr tracers on day 1. D3-3MH was consumed on day 3, 24h prior to returning to the lab. From urine, saliva and blood samples, and a single muscle biopsy (vastus lateralis), we determined muscle mass, MPS and MPB. D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r = 0.69, P = 0.027). Rates of cumulative myofibrillar MPS over 3days were 0.072%/h (95% CI, 0.064 to 0.081%/h). Whole-body MPB over 6h was 0.052 (95% CI, 0.038 to 0.067). These rates were similar to previous literature. We demonstrate the potential for D3-Cr to be used alongside D2O and D3-3MH for concurrent measurement of muscle mass, MPS, and MPB using a minimally invasive design, applicable for clinical and frail populations.

Citation

Cegielski, J., Wilkinson, D. J., Brook, M. S., Boereboom, C., Phillips, B. E., Gladman, J. F. R., Smith, K., & Atherton, P. J. (2021). Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a ‘Combined Oral Stable Isotope Assessment of Muscle (COSIAM)’ approach. GeroScience, 43(6), 2653-2665. https://doi.org/10.1007/s11357-021-00386-2

• Journal Article Type: Article
• Acceptance Date: May 17, 2021
• Online Publication Date: May 27, 2021
• Publication Date: May 27, 2021
• Deposit Date: Jun 9, 2021
• Publicly Available Date: Jun 9, 2021
• Journal: GeroScience
• Print ISSN: 2509-2715
• Electronic ISSN: 2509-2723
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 43
• Issue: 6
• Pages: 2653-2665
• DOI: https://doi.org/10.1007/s11357-021-00386-2
• Public URL: https://nottingham-repository.worktribe.com/output/5652273
• Publisher URL: https://link.springer.com/article/10.1007/s11357-021-00386-2