Senescent cells secrete chromatin components via senescence-associated extracellular particles
Peter Adams1,2, Sviatlana Zaretski1,3, Jose L Nieto Torres1
1Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037.
Research Square
|February 6, 2026
Summary
Senescent cells release DNA and proteins via extracellular particles, activating inflammatory pathways in other cells. Inhibiting autophagy increases this release, highlighting a new signaling mechanism in aging.
Area of Science:
- Cellular senescence
- Extracellular vesicles
- Inflammation
Background:
- Senescent cells secrete SASP, including CCFs that activate cGAS/STING.
- Autophagy degrades CCFs, but their extracellular fate is unknown.
Purpose of the Study:
- Investigate the extracellular release and signaling of CCF components from senescent cells.
- Characterize the morphology and function of CCF-containing extracellular particles.
Main Methods:
- Analysis of extracellular particle release from senescent cells.
- Characterization of secreted CCF components (ɣH2AX, dsDNA).
- Assessment of cGAS-STING pathway activation in recipient cells.
- Detection of CCF particles in aged mouse circulation.
Main Results:
- Senescent cells release CCF components (ɣH2AX, dsDNA) via multivesicular bodies.
- Secreted CCFs form unique "popcorn"-like extracellular particles.
- Autophagy inhibition increases CCF particle secretion.
- Extracellular CCF particles activate cGAS-STING in non-senescent cells and are found in aged mice.
Conclusions:
- Senescent cells release CCF components via a novel extracellular pathway.
- These extracellular CCF particles represent a new mode of intercellular signaling.
- The findings link cellular senescence, extracellular vesicles, and inflammation in aging.
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