Suppression of Ciliogenesis Alleviates Cellular Senescence via AKT Signaling in Gingival Aging.

Abstract

Aging, as an intrinsic risk factor, accelerates gingival inflammation and periodontal diseases. However, the cellular and molecular mechanisms underlying gingival aging remain unclear, hindering the development of targeted therapies. In this study, we performed the first single-cell transcriptomic analysis of aging human gingiva, identifying primary cilia as potential regulators of gingival fibroblast senescence. We demonstrated that aged gingival tissues exhibit increased fibroblast senescence and enhanced ciliogenesis compared to young tissues. Suppression of ciliogenesis significantly reduced senescence markers and alleviated DNA damage in aged fibroblasts accompanied by increased AKT activation. In addition, FOXO1 inactivation and enhanced expression of DNA repair-related genes were found after suppression of ciliogenesis in aged gingival fibroblasts. Importantly, inhibition of AKT partially reversed the anti-senescent phenotypes induced by ciliogenesis suppression. Functionally, adeno-associated virus-mediated suppression of ciliogenesis in aged mice mitigated gingival fibroblast senescence, reduced inflammation, and diminished tissue fibrosis. These findings highlight that primary cilia may contribute to the regulation of gingival fibroblast senescence and identify ciliary dynamics and AKT signaling downstream of cilia as potential therapeutic targets for managing aging-related gingival diseases, providing a potential strategy to improve periodontal health in the elderly.