{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:30:35Z","timestamp":1786696235877,"version":"build-2736575974"},"reference-count":164,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>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 \u201cprotein aging modules\u201d\u2014including inflammatory cytokines, chemokines, complement proteins, and ECM-modifying enzymes\u2014may 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.<\/jats:p>","DOI":"10.3389\/fragi.2026.1895104","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:08:57Z","timestamp":1786694937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomics of aging: biomarkers for physiological systems and diseases"],"prefix":"10.3389","volume":"7","author":[{"given":"Ying","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology","place":["Guangzhou, China"]},{"name":"RayBiotech Co., Ltd.","place":["Guangzhou, China"]},{"name":"South China Biochip Research Center","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Lin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"China-UK Joint Laboratory on Health and Ageing Research","place":["Guangzhou, China"]},{"name":"Infinitus (China) Company Ltd.","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjue","family":"Wang","sequence":"additional","affiliation":[{"name":"RayBiotech Co., Ltd.","place":["Guangzhou, China"]},{"name":"South China Biochip Research Center","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Luo","sequence":"additional","affiliation":[{"name":"South China Biochip Research Center","place":["Guangzhou, China"]},{"name":"RayBiotech Inc.","place":["Peachtree Corners, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology","place":["Guangzhou, China"]},{"name":"National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR)","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo-Pan","family":"Huang","sequence":"additional","affiliation":[{"name":"RayBiotech Co., Ltd.","place":["Guangzhou, China"]},{"name":"South China Biochip Research Center","place":["Guangzhou, China"]},{"name":"RayBiotech Inc.","place":["Peachtree Corners, GA, United States"]},{"name":"Affiliated Cancer Hospital and Institute of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.20517\/jca.2025.14","article-title":"Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions","volume":"5","author":"Adhikari","year":"2025","journal-title":"J. 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