{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:31:44Z","timestamp":1789659104830,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,13]]},"group-title":"Systems Biology","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["American Federation for Aging Research and Glenn Foundation Award for Junior Faculty"],"award-info":[{"award-number":["American Federation for Aging Research and Glenn Foundation Award for Junior Faculty"]}],"id":[{"id":"https:\/\/ror.org\/000r61a05","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of General Medical Sciences","award":["R35GM155447"],"award-info":[{"award-number":["R35GM155447"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["R21AG067368"],"award-info":[{"award-number":["R21AG067368"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["R21AG067368-02S1"],"award-info":[{"award-number":["R21AG067368-02S1"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Dysfunctional monocyte states contribute to age-related pathologies and systemic inflammation. However, the gene regulatory networks governing the transition to these states remain unknown. Here we used bulk and single-cell multidimensional integrative profiling to reveal previously uncharacterized monocyte state transitions during human aging. We show that a transient senescent-like population arising from classical CD14\n                  <jats:sup>++<\/jats:sup>\n                  CD16\n                  <jats:sup>-<\/jats:sup>\n                  monocytes drives the accumulation of an inflammatory monocyte state in aging humans. This senescence-associated transition is orchestrated by the master senescence regulator AP-1, which acts on a pre-established chromatin landscape to rewire the monocyte transcription factor (TF) network and activate both senescence\u2013 and age-associated inflammatory transcriptional programs. Through integration with clinical transcriptomic datasets, we demonstrate that senescent-like and aged monocytes are transcriptionally primed toward sepsis-associated states. Overall, our study provides the core gene-regulatory principles underlying a senescent-like transitional state in monocytes and identifies AP-1 as an attractive target to modulate systemic inflammation in age and disease.\n                <\/jats:p>","DOI":"10.64898\/2026.09.09.750459","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T11:20:12Z","timestamp":1789298412000},"source":"Crossref","is-referenced-by-count":0,"title":["A transitional senescence program drives inflammatory monocyte state expansion in aging humans"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1962-5073","authenticated-orcid":false,"given":"Themistoklis","family":"Vasilopoulos","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, 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