PDF(Pubmed)
Abstract：
The prevalence of periodontitis increases with physiological aging. However, whether bacteria associated with periodontal diseases foster aging and the mechanisms by which they may do so are unknown. Herein, we hypothesize that Fusobacterium nucleatum, a microorganism associated with periodontitis and several other age-related disorders, triggers senescence, a chief hallmark of aging responsible to reduce tissue repair capacity. Our study analyzed the senescence response of gingival epithelial cells and their reparative capacity upon long-term exposure to F. nucleatum. Specifically, we assessed (a) cell cycle arrest by analyzing the cyclin-dependent kinase inhibitors p16INK4a and p14ARF and their downstream cascade (pRb, p53, and p21) at both gene and protein levels, (b) lysosomal mediated dysfunction by using assays targeting the expression and activity of the senescence-associated β-galactosidase (SA-β-Gal) enzyme, and (c) nuclear envelope breakdown by assessing the expression of Lamin-B1. The consequences of the senescence phenotype mediated by F. nucleatum were further assessed using wound healing assays. Our results revealed that prolonged exposure to F. nucleatum promotes an aging-like phenotype as evidenced by the increased expression of pro-senescence markers (p16INK4a , p21, and pRb) and SA-β-Gal activity and reduced expression of the counter-balancing cascade (p14ARF and p53) and Lamin-B1. Furthermore, we also noted impaired wound healing capacity of gingival epithelial cells upon prolong bacterial exposure, which was consistent with the senescence-induced phenotype. Together, our findings provide a proof-of-concept evidence that F. nucleatum triggers a pro-senescence response in gingival epithelial cells. This might affect periodontal tissue homeostasis by reducing its repair capacity and, consequently, increasing susceptibility to periodontitis during aging.
摘要：
牙周炎的患病率随着生理老化而增加。然而,与牙周疾病相关的细菌是否促进衰老以及它们可能促进衰老的机制尚不清楚。在这里，我们假设有核梭杆菌,一种与牙周炎和其他一些与年龄有关的疾病有关的微生物，引发衰老,衰老的主要标志，负责降低组织修复能力。我们的研究分析了长期暴露于核仁F.后牙龈上皮细胞的衰老反应及其修复能力。具体来说,我们通过分析细胞周期蛋白依赖性激酶抑制剂p16INK4a和p14ARF及其下游级联反应（pRb，p53和p21）在基因和蛋白质水平上，(b)通过使用针对衰老相关β-半乳糖苷酶(SA-β-Gal)酶的表达和活性的测定,溶酶体介导的功能障碍,和(c)通过评估Lamin-B1的表达来破坏核包膜。使用伤口愈合测定进一步评估由核仁F.介导的衰老表型的后果。我们的结果表明，长时间暴露于F.nucleatum促进了衰老样表型，如通过促衰老标记的表达增加所证明的（p16INK4a，p21和pRb）和SA-β-Gal活性以及平衡级联（p14ARF和p53）和Lamin-B1的表达降低。此外，我们还注意到牙龈上皮细胞在延长细菌暴露后伤口愈合能力受损，这与衰老诱导的表型一致。一起,我们的研究结果提供了一个概念证据,证明核仁F.在牙龈上皮细胞中触发了促衰老反应.这可能通过降低牙周组织的修复能力来影响牙周组织的稳态，因此,在衰老过程中对牙周炎的易感性增加。
