Assessment of a low skeletal muscle mass (SM) is important for diagnosis of ageing and disease-associated sarcopenia and is hindered by heterogeneous methods and terminologies that lead to differences in diagnostic criteria among studies and even among consensus definitions. The aim of this review was to analyze and summarize previously published cut-offs for SM applied in clinical and research settings and to facilitate comparison of results between studies. Multiple published reference values for discrepant parameters of SM were identified from 64 studies and the underlying methodological assumptions and limitations are compared including different concepts for normalization of SM for body size and fat mass (FM). Single computed tomography or magnetic resonance imaging images and appendicular lean soft tissue by dual X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) are taken as a valid substitute of total SM because they show a high correlation with results from whole body imaging in cross-sectional and longitudinal analyses. However, the random error of these methods limits the applicability of these substitutes in the assessment of individual cases and together with the systematic error limits the accurate detection of changes in SM. Adverse effects of obesity on muscle quality and function may lead to an underestimation of sarcopenia in obesity and may justify normalization of SM for FM. In conclusion, results for SM can only be compared with reference values using the same method, BIA- or DXA-device and an appropriate reference population. Limitations of proxies for total SM as well as normalization of SM for FM are important content-related issues that need to be considered in longitudinal studies, populations with obesity or older subjects.

The historical 1975 Reference Man is a ‘model’ that had been used as a basis for the calculation of radiation doses, metabolism, pharmacokinetics, sizes for organ transplantation and ergonomic optimizations in the industry, e.g., to plan dimensions of seats and other formats. The 1975 Reference Man was not an average individual of a population; it was based on the multiple characteristics of body compositions that at that time were available, i.e., mainly from autopsy data. Faced with recent technological advances, new mathematical models and socio-demographic changes within populations characterized by an increase in elderly and overweight subjects a timely ‘state-of-the-art’ 2021 Reference Body are needed. To perform this, in vivo human body composition data bases in Kiel, Baton Rouge, San Francisco and Honolulu were analyzed and detailed 2021 Reference Bodies, and they were built for both sexes and two age groups (≤40 yrs and >40 yrs) at BMIs of 20, 25, 30 and 40 kg/m². We have taken an integrative approach to address ‘structure–structure’ and ‘structure–function’ relationships at the whole-body level using in depth body composition analyses as assessed by gold standard methods, i.e., whole body Magnetic Resonance Imaging (MRI) and the 4-compartment (4C-) model (based on deuterium dilution, dual-energy X-ray absorptiometry and body densitometry). In addition, data obtained by a three-dimensional optical scanner were used to assess body shape. The future applications of the 2021 Reference Body relate to mathematical modeling to address complex metabolic processes and pharmacokinetics using a multi-level/multi-scale approach defining health within the contexts of neurohumoral and metabolic control.