Senescent cells maintain viability through adhesion-dependent fragmentation that promotes debris deposition.

Matej Durik, Mona Karout, Daniel Sampaio Gonçalves, Tania Knauer-Meyer, Coralie Spiegelhalter, Nadia Messaddeq, Marco Seehawer, Pauline Stephan, Dmitry V Bulavin, Yann Herault, Lars Zender, William M Keyes

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Équipe Labellisée Ligue Contre le Cancer, Illkirch, France; UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France; U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France; Université de Strasbourg, Illkirch, France. Electronic address: [email protected] de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Équipe Labellisée Ligue Contre le Cancer, Illkirch, France; UMR7104, Centre National de la Recherche Scientifique (CNRS), Illkirch, France; U1258, Institut National de la Santé et de la Recherche Médicale (INSERM), Illkirch, France; Université de Strasbourg, Illkirch, France. Electronic address: [email protected]. · pubmed

Paper

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 through cell-to-cell adhesion, which we term "senescent-cell adhesion fragments" (SCAFs). Found in many senescent states, including human and mouse cells, and mouse tissues, SCAFs lack nuclear material but contain organelles, including damaged mitochondria. Disrupting adherens junctions decreases SCAF formation but induces senescent-cell death, due to an inability to shed damaged mitochondria. Live imaging and proteomics 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. Immunostaining also reveals amyloid-like material in senescent cells that can be externalized through fragmentation. Altogether, these findings identify a feature that facilitates senescent cell survival but also externally deposits damaged intracellular contents, with implications for cancer and neurodegeneration.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

Senescent cells maintain viability by shedding damaged organelles via adhesion-dependent fragmentation (SCAFs), a process that prevents cell death but releases DAMPs and amyloid-like material that drives inflammation and disease. This is relevant because it identifies a specific mechanism of senescent cell survival and a novel source of age-related tissue damage (debris deposition) that could be targeted to enhance senolytic efficacy or reduce the pro-aging secretory phenotype without necessarily killing the cell.

Author of this paper? Send a correction.