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bioRxiv · 10.1101/2023.01.11.523642

Senescent cells deposit intracellular contents through adhesion-dependent fragmentation

Durik, M.·Sampaio Goncalves, D.·Spiegelhalter, C.·Messaddeq, N.·Keyes, B.
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Abstract

Cellular senescence is a state of stable arrest and secretion linked to aging and disease. Here we identify that senescent cells dispose of large fragments of themselves through cell-to-cell adhesion, which we term senescent-cell adhesion fragments (SCAFs). Found across all senescent types examined, SCAFs lack nuclear material but contain organelles, including damaged mitochondria. Disrupting adherens junctions decreased SCAF formation but induced senescent-cell death, which was caused by an inability to shed damaged mitochondria. Dynamic analyses show that SCAFs ultimately rupture, releasing a complex proteome including damage-associated molecular patterns (DAMPs) and proteins linked to neurodegenerative disease. Functionally, SCAFs activate wound-healing and cancer-related programs, promoting migration and invasion. Altogether, these findings identify a new feature that facilitates senescent cell survival, but the consequence of which is external deposition of damaged intracellular contents, with implications for cancer and aging.

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Durik, M., Sampaio Goncalves, D., Spiegelhalter, C., Messaddeq, N., Keyes, B.. 2023-01-12. Senescent cells deposit intracellular contents through adhesion-dependent fragmentation. https://doi.org/10.1101/2023.01.11.523642

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