{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:24Z","timestamp":1787120844986,"version":"build-2736575974"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is characterized by chronic immune activation and molecular alterations that overlap with aging-related biological processes. However, how these alterations are organized across molecular layers and whether they converge on shared regulatory networks remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed an integrative multi-omics analysis combining in-house proteomic and phosphoproteomic data from 130 patients with SLE and 90 healthy controls (HCs) and publicly available transcriptomic datasets comprising 1,461 SLE patients. Proteins and phosphorylation sites were annotated using established aging-related gene resources. Differential protein abundance and phosphorylation changes were analyzed across disease-status and disease-activity comparisons. Nominal\n                      <jats:italic>P<\/jats:italic>\n                      -value thresholds were used for exploratory feature selection, whereas FDR-adjusted\n                      <jats:italic>P<\/jats:italic>\n                      values were used to assess robustness after multiple-testing correction. Kinase-substrate enrichment, transcription factor annotation, and cell-type-resolved transcriptomic comparison were used to explore potential regulatory programs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 128 nominally altered proteins annotated to aging-related biological processes, including genomic instability, mitochondrial dysfunction, and epigenetic alterations. Phosphoproteomic analysis revealed 36 nominally altered phosphorylation sites, including previously unreported sites in IFI16 (S153, S780) and PKC\u03b4 (S507, S664). Clustering analysis demonstrated heterogeneous protein co-regulation patterns across disease states. Kinase activity inference suggested altered activity of TBK1 and IKK\u03b2. TF analysis further highlighted STAT1, RELA, and PML as potential central nodes within the inferred regulatory network. Notably, these multi-omic alterations were not randomly distributed but showed convergence toward shared signaling pathways, particularly those related to interferon responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative multi-omics study identifies inflammatory and interferon-dominated molecular alterations in SLE PBMCs that overlap with aging-related biological processes and converge on shared regulatory networks. These findings provide a hypothesis-generating framework for investigating the intersection between chronic immune activation and aging-related molecular remodeling in SLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1861904","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:45:33Z","timestamp":1787118333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-omics profiling identifies aging-related molecular signatures and convergent interferon signaling in systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongwei","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Shenzhen Hospital","place":["Shenzhen, China"]},{"name":"Department of Experimental Research, South China Hospital, Medical School, Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donge","family":"Tang","sequence":"additional","affiliation":[{"name":"Clinical Medical Research Center, The First Affiliated Hospital (Shenzhen People\u2019s Hospital), Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Dai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Medicine, Anhui University of Science and Technology","place":["Huainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of GCP, The Third People\u2019s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Shenzhen Hospital","place":["Shenzhen, China"]},{"name":"Department of Experimental Research, South China Hospital, Medical School, Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01898-7","article-title":"The immunology of systemic lupus erythematosus","volume":"25","author":"Tsokos","year":"2024","journal-title":"Nat Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2174\/1874609808666150727111904","article-title":"Aging and systemic lupus erythematosus - immunosenescence and beyond","volume":"8","author":"van den Hoogen","year":"2015","journal-title":"Curr Aging 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