{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:28:51Z","timestamp":1786512531103,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,10]]},"group-title":"Cell Biology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["U54 AG079754, U54 AG079758, UH3 CA275669"],"award-info":[{"award-number":["U54 AG079754, U54 AG079758, UH3 CA275669"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The liver is organized into tightly regulated zones with distinct metabolic functions but zonation erodes with age. Cellular senescence contributes to aging and liver diseases, however, its impact on aging biology is ill-defined. As part of The Cellular Senescence Network Consortium, we used multiple spatial transcriptomics approaches (GeoMx, Visium, CosMx) with snRNA-seq to profile senescence signatures, zonation markers, and metabolic pathways in livers from wild-type (WT) mice of multiple ages. We observed a loss of canonical zone signatures in aged mouse livers characterized by \u201cexpansion\u201d of midlobular (zone 2) marker gene expression, accompanied by diminished expression of zone 3 marker genes by middle-age (18 months), indicative of loss of cell identity. Multiple analytic approaches identified distinct age-, zone- and sex-specific senescence signatures, which were significantly associated with zonation markers changes. This was recapitulated in\n                  <jats:italic>Ercc1<\/jats:italic>\n                  mutant models of accelerated senescence, supporting a causal role of senescent cells in liver aging. A \u201cno-zone\u201d hepatocyte-like cluster expanded with age and with the strongest Senescence-Associated Secretory Phenotype (SASP) profile. Gene expression profiles from senescent hepatocytes implicate decreased WNT signaling and increased BMP as contributing to age-related loss of zonation. Together, these data elucidate the role of senescent cells in driving aging biology in non-diseased liver through disruption of cell:cell signaling and the loss of metabolic and cell identity gene expression necessary for hepatocyte function.\n                <\/jats:p>","DOI":"10.64898\/2026.08.08.743614","type":"posted-content","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:25:23Z","timestamp":1786375523000},"source":"Crossref","is-referenced-by-count":0,"title":["Cellular senescence is associated with age-related loss of liver zonation and hepatocyte function"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3796-8847","authenticated-orcid":false,"given":"Linshan","family":"Laux","sequence":"first","affiliation":[{"name":"Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United States"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Aristel","sequence":"additional","affiliation":[{"name":"Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute for Health Informatics, University of Minnesota, Minneapolis, MN, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Lande","sequence":"additional","affiliation":[{"name":"Salk Institute for Biological Studies, Integrative Genomics and Bioinformatics Core, La Jolla, CA, USA"},{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyi","family":"Li","sequence":"additional","affiliation":[{"name":"Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, United States"},{"name":"Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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