Senescent cells deposit intracellular contents through adhesion-dependent fragmentation

Abstract

ABSTRACTCellular senescence is a complex cell state with roles in tumor suppression, embryonic development and wound repair. However, when misregulated, senescence contributes to aging and disease. Here we identify that senescent cells generate/break off large membranebound fragments of themselves through cell-to-cell adhesion. We designate these as senescent-cell adhesion fragments (SCAFs) which were present in all types of senescent cell examined. We show they contain many organelles from the original cell, but without nuclear material. Quantitative and dynamic profiling shows that SCAFs are large, may persist for a number of days, but rupture and release their contents onto neighboring cells. Protein profiling identifies that SCAFs contain a complex proteome including immune recruitment factors and damage-associated molecular patterns (DAMPs). Functional studies reveal that SCAFs activate signatures related to wound healing and cancer, and promote invasion and migration. Altogether, we uncover an additional cellular feature of senescent cells, by which they deposit intracellular contents on other cells. We speculate this may aid in boosting immune responses, but in chronic situations, may contribute to debris buildup, inflammaging and age-associated changes.