Senescent cells secrete chromatin components via senescence-associated extracellular particles

Senescent cells secrete chromatin components via senescence-associated extracellular particles | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Senescent cells secrete chromatin components via senescence-associated extracellular particles Peter Adams, Sviatlana Zaretski, Jose L. Nieto Torres, Xue Lei, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8349343/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Senescent cells influence their surroundings through the senescence-associated secretory phenotype (SASP), an assortment of secreted molecules and macromolecular complexes. Among SASP’s intracellular drivers are cytoplasmic chromatin fragments (CCFs), nuclear-derived DNA that activates the pro-inflammatory cGAS/STING pathway. While autophagy contributes to CCFs degradation, the full repertoire of CCF fates and signaling functions remains unclear. Here, we show that senescent cells release CCF components, ɣH2AX and double-stranded DNA (dsDNA), into the extracellular space via an ESCRT-independent multivesicular body pathway. Secreted CCF components localize to extracellular particles exhibiting an unusual “popcorn”-like morphology, distinct from canonical small extracellular vesicles. Notably, inhibition of autophagy enhances secretion of CCF components and particles, suggesting an inverse relationship between intracellular clearance and extracellular release. A fraction of CCF-containing extracellular particles activates cGAS-STING signaling in non-senescent proliferating cells and is enriched in the circulation of aged mice, pointing to a previously unrecognized mode of extracellular signaling by senescent cells. Biological sciences/Cell biology/Senescence Biological sciences/Cell biology/Cell signalling/Extracellular signalling molecules Biological sciences/Cell biology/Autophagy/Macroautophagy senescence cytoplasmic chromatin fragments secretory particles Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8349343","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":571684626,"identity":"f110a1ef-b46b-4479-b416-7cebcbf9b226","order_by":0,"name":"Peter Adams","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYHACAyC2AZEGB0jRkka6lsNgLcSpN2c/vPHTjT/n7c2lmzce/FFjk9gvfcaA4eOeWpxaLHvSiqVz224n7pxzrOAwz7G0xJl9OQaMM54dx+2qAzkG0rkNtxMMbuQYHGZsOGxscIbHgJnnwDHcWs6/Mf6d8+ecPUjLwZ9ALfYEtdzIMZPOYTvAuAGo5QBvw2E5Ax6wlhrcfpnxrMw6ty0Z7hc5iTNsBQdnHDiAU4s5f/Lm2zl/7EAhtvkjMMR4+HuYNz74cKAOt8PgLAk4iwMUp4dJ0sL+AEjgtmUUjIJRMApGHAAAptddNdjjouQAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0684-1770","institution":"Sanford Burnham Prebys Medical Discovery Institute","correspondingAuthor":true,"prefix":"","firstName":"Peter","middleName":"","lastName":"Adams","suffix":""},{"id":571684627,"identity":"d390c010-926f-448d-8327-7c2e88c7bc3f","order_by":1,"name":"Sviatlana Zaretski","email":"","orcid":"","institution":"Sanford Burnham Prebys Medical Discovery Institute","correspondingAuthor":false,"prefix":"","firstName":"Sviatlana","middleName":"","lastName":"Zaretski","suffix":""},{"id":571684628,"identity":"b9d941b9-9df5-4e69-aa72-f3a652013567","order_by":2,"name":"Jose L. 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