Proteomics of Aging: Biomarkers for Physiological Systems and Diseases

Aging is a complex, multifaceted process that affects various physiological systems, including the immune, metabolic/endocrine, cardiovascular, musculoskeletal, and nervous systems. The proteomic landscape of aging reveals a dynamic interplay between these systems, with age-related changes in circulating proteins reflecting biological rather than chronological aging. This review aims to synthesize current evidence on proteomic biomarkers across major physiological systems, highlighting shared molecular signatures that underpin multisystem decline. Key biomarkers include IL-6, CRP, CXCL9/10, GDF15, IGF-1, VCAM-1, NT-proBNP, NfL, and GFAP, which track inflammatory activation, mitochondrial and metabolic stress, extracellular matrix remodeling, and neuro-glial injury. The use of proteomic aging clocks, which leverage dozens to hundreds of circulating proteins, has been shown to predict frailty, multimorbidity, organ-specific biological age, and mortality with high accuracy in large population cohorts. Emerging evidence suggests that a limited set of cross-system protein aging modules may serve as integrative readouts and potential regulators of aging biology. Methodological advances, system-specific mechanisms, and translational applications of proteomic aging models are discussed. These findings position proteomics as a powerful tool for quantifying biological age, identifying early disease risk, and guiding precision interventions to promote healthier aging. However, it is essential to note that these findings are based on research-use-only laboratory peptides and should not be used for clinical applications without further validation and regulatory approval.