Proteomic ageing clocks: methods, mechanisms and the muscle connection

Abstract Proteomic ageing clocks are emerging tools that estimate biological age from protein abundance patterns. Most models are developed using blood capturing inflammatory, metabolic, and extracellular proteins, including secreted signalling factors. Large-scale plasma studies now predict chronological age, disease risk and mortality, but muscle-related models remain indirect, relying on organ-enriched circulating proteins rather than biopsy-derived skeletal muscle clocks. We review current proteomic clock frameworks, computational approaches, platform considerations and validation strategies, highlighting the potential of muscle-based clocks to capture tissue and subcellular-specific ageing processes. We discuss future integration of spatial, single-cell, and multi-omic data to enhance mechanistic insight and translational relevance.