Frontiers in Medicine · Oct 14, 2026

A research framework for evaluating upstream multimodal sarcopenia risk domains in older adults

By Kim N

Established sarcopenia definitions identify clinically important impairment, but their thresholds are not designed to characterize all biological changes associated with subsequent muscle decline. Whether additional measurements improve assessment before these thresholds are reached remains uncertain. This structured narrative review proposes a research framework for evaluating upstream, multimodal sarcopenia risk domains in older adults. It integrates diagnostic consensus statements with mechanistic, observational, diagnostic-accuracy, prognostic, and intervention literature identified through purposive searches and citation tracking. Candidate domains comprise circulating biomarkers, creatine-pool-based muscle mass estimation, neuromuscular measurements, imaging and bioelectrical measures, and digital mobility assessments. The evidence supporting these domains is heterogeneous. Cross-sectional differences and biological plausibility do not establish prediction of incident sarcopenia, incremental clinical value, or differential treatment benefit. Neuromuscular abnormalities may reflect aging rather than sarcopenia specifically, and measures commonly grouped as muscle quality assess distinct constructs. The proposed domains are therefore nonexclusive and nonsequential; no diagnostic stages, validated multimodal score, or biomarker-guided treatment algorithm are proposed. Conventional clinical assessments provide reference phenotypes, while falls, disability, fractures, quality of life, hospitalization, and mortality remain separate validation outcomes. The principal contribution is an evidence-to-validation framework that distinguishes demonstrated measurement capabilities from untested applications. Priorities are longitudinal assessment, reproducibility, external validation, incremental prediction beyond inexpensive clinical measures, and trials of clinical utility before implementation.

doi.org/10.3389/fmed.2026.1928432Open accessPubMed 42953499Biomarkers