Proteomics of aging: biomarkers for physiological systems and diseases

Abstract

Aging is a progressive, multisystem process characterized by declining physiological resilience and increased susceptibility to chronic diseases. Recent advances in high-throughput proteomics have enabled comprehensive mapping of age-related changes across circulating proteins, revealing dynamic and non-linear trajectories that reflect biological rather than chronological aging. This review synthesizes current evidence on proteomic biomarkers across major physiological systems, including the immune, metabolic/endocrine, cardiovascular, musculoskeletal, and nervous systems, and highlights shared molecular signatures that underpin multisystem decline. Robust biomarkers such as IL-6, CRP, CXCL9/10, GDF15, IGF-1, VCAM-1, NT-proBNP, NfL, and GFAP consistently track inflammatory activation, mitochondrial and metabolic stress, extracellular matrix remodeling, and neuro-glial injury. Large population cohorts demonstrate that proteomic aging clocks, leveraging dozens to hundreds of circulating proteins, can predict frailty, multimorbidity, organ-specific biological age, and mortality with high accuracy. Emerging evidence suggests that a limited set of cross-system “protein aging modules”—including inflammatory cytokines, chemokines, complement proteins, and ECM-modifying enzymes—may serve as integrative readouts and potential regulators of aging biology. We discuss methodological advances, system-specific mechanisms, and translational applications of proteomic aging models. Together, these findings position proteomics as a powerful tool for quantifying biological age, identifying early disease risk, and guiding precision interventions to promote healthier aging.