Introduction: With increased lifespan associating with age-related muscle loss (sarcopenia), optimising approaches for quantifying skeletal muscle ‘health biomarkers’ (i.e. muscle mass, muscle protein synthesis (MPS) and breakdown (MPB)) remains a major need. Further, any such methods must be broadly applicable, minimally-invasive, robust and cost-effective if they are to be used for comprehending, and developing treatments relating to mitigating age-related loss of muscle mass. Currently, technical approaches for measurement of MPS/MPB are time-limited, require the infusion of expensive sterile isotopically labelled tracers, and involve blood and tissue sampling under sterile conditions. Similarly, muscle mass imaging methods (e.g. MRI, CT, DXA), while minimally-invasive, are costly and not readily accessible. Aim: First, to develop a combinatorial approach to concurrently quantify muscle mass and muscle protein turnover (i.e. MPS and MPB) using the stable-isotope tracers D3-creatine (D3-Cr)1, deuterium oxide (D2O)2, and D3-3-methylhistidine (D3-3MH)3, respectively; second, to uncover novel relationships between skeletal muscle mass/strength and MPS/MPB. Methods: We recruited 10 older men (~70y, BMI: ~25kg.m-2) into a 4-day study, with a DXA and D3-Cr being orally consumed (dissolved in D2O) on day 1. D3-3MH was provided (single tube, dissolved in water) to be taken home and consumed on day 3. From timed urine, saliva, blood samples and one muscle biopsy (m. vastus lateralis, VL) on day 4, we determined muscle mass, MPS and MPB via mass spectrometry. Additionally, we assessed leg power (Nottingham Rig), strength (1-RM) and handgrip strength (dynamometry).Results: D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r=0.69, P=0.013), leg strength (D3-Cr: r=0.64, P=0.0234) and leg power (D3-Cr: r=0.67, P=0.017). There were no correlations between whole-body muscle mass and cumulative myofibrillar protein synthesis (FSR; representative of VL MPS) measured over the 4-days, or whole-body MPB. However, FSR had a positive trend with muscle mass (D3-Cr: r=0.52, P=0.12, AFFM: r= 0.50, P=0.072). Furthermore, FSR positively correlated with leg power (r=0.56, P=0.0455); and had a significantly negative correlation with handgrip strength (r=-0.74, P=0.007). Conclusions: We demonstrate the efficacy of COSIAM for concurrent measurement of MPS, MPB and muscle mass in humans. The COSIAM approach is minimally-invasive and has broad applicability to wider clinical, frailty and care home studies. Moreover, COSIAM uncovered novel relationships linking cumulative deficits in MPS to muscle function and potentially age-related muscle loss. A larger cohort will be required to investigate these relationships further.