Characterization of senescence and nuclear reorganization in aging gingival cells.

Abstract

Cellular senescence is a stress response that limits tumor formation by promoting the removal of damaged cells through the immune system. In this study, we observed accumulation of senescent cells during human aging gingival tissue, by increased levels of γH2A.X, 53BP1, and SAHF, along with a greater distance of H3K9me3 from the nuclear periphery. Additionally, primary gingival fibroblasts from older individuals displayed an enlarged nuclear area and perimeter, accompanied by DNA damage responses and increased Lamin B1 invaginations. The combination of phospho-p38 (Thr180/Tyr182) foci with form factor demonstrated an 79.27% predictive accuracy for aging in gingival fibroblasts, with an AUC of 0.83. In co-culture experiments, our findings revealed that senescent fibroblasts from aged donors exhibit slower and fewer recruitment of PBMCs and decreased levels of the Natural Killer cell receptor ligand MICA/B and the CD112R ligand Nectin-2, suggesting potential impairment in immune surveillance mechanisms during aging.