{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:44:20Z","timestamp":1792046660819,"version":"4.4.0"},"posted":{"date-parts":[[2026,9,10]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Aging","award":["RF1AG072602 \/ R01AG072602"],"award-info":[{"award-number":["RF1AG072602 \/ R01AG072602"]}]},{"name":"2021 F Tobacco CURE Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,14]]},"abstract":"<jats:p>Genome maintenance is usually treated as cell-intrinsic, yet brain cells age within multicellular neighborhoods. Whether a cell's DNA damage response (DDR) state is systematically embedded in native tissue architecture is unknown. We used MERFISH to map curated repair programs across 604,252 cells in matched sections from 2-3 and 22-month-old mice. Regional DDR expression and coordination formed an age-dependent mosaic, accompanied by immune and oligodendroglial shifts. Independent metacell and distance-resolved analyses identified a consistent anchor-dependent organization. Low-DDR neurons occupied immune- and OPC-oligodendroglial-rich niches. In contrast, DDR-high vascular anchors were associated with vascular-cell enrichment and, in cortex and cerebral nuclei, OPC-oligodendroglial enrichment, whereas immune cells were enriched around DDR-low vascular anchors. Thus, genome-maintenance state was associated with distinct anchor-cell-specific spatial context depending on anchor-cell identity and its DDR transcriptional state. These opposing neuronal and vascular patterns define anchor-dependent genome-maintenance niches as a spatial feature of brain aging, with implications for regional vulnerability.<\/jats:p>","DOI":"10.64898\/2026.09.07.749801","type":"posted-content","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:15:11Z","timestamp":1789067711000},"source":"Crossref","is-referenced-by-count":0,"title":["Neuronal and vascular genome-maintenance states organize opposing multicellular architectures in the aging brain"],"prefix":"10.64898","author":[{"given":"Arvin","family":"Koshboresh","sequence":"first","affiliation":[{"name":"Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay Laxmi","family":"Roy","sequence":"additional","affiliation":[{"name":"Penn State University College of Medicine, Neuroscience and Experimental Therapeutics Department, Hershey, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-4296","authenticated-orcid":false,"given":"Mofida","family":"Abdelmageed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-6833","authenticated-orcid":false,"given":"Steffy B","family":"Manjila","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-3893","authenticated-orcid":false,"given":"Deniz","family":"Parmaksiz","sequence":"additional","affiliation":[{"name":"Penn State University College of Medicine, Neuroscience and Experimental Therapeutics Department, Hershey, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-0279","authenticated-orcid":false,"given":"Yongsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Penn State University College of Medicine, Neuroscience and Experimental Therapeutics Department, Hershey, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-9774","authenticated-orcid":false,"given":"Jesse","family":"Gillis","sequence":"additional","affiliation":[{"name":"Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5347-9260","authenticated-orcid":false,"given":"Anirban","family":"Paul","sequence":"additional","affiliation":[{"name":"Penn State University College of Medicine, Neuroscience and Experimental Therapeutics Department, Hershey, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.07.749801","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:55:19Z","timestamp":1792043719000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.07.749801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.09.07.749801","relation":{},"subject":[],"published":{"date-parts":[[2026,9,10]]},"subtype":"preprint"}}