Department of Spine Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Medical Department, Baoshan Branch of Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Aging (Albany NY). 2021 Feb 10;13(4):6025-6040. doi: 10.18632/aging.202536.
Lumbar spinal stenosis (LSS) is a condition wherein patients exhibit age-related fibrosis, elastin-to-collagen ratio reductions, and ligamentum flavum hypertrophy. This study was designed to assess the relationship between SIRT6 and telomerase activity in hypertrophic ligamentum flavum (LFH) cells from LSS patients. We observed significant reductions in SIRT6, TPP1, and POT1 protein levels as well as increases in telomerase reverse transcriptase (TERT) levels and telomerase activity in LFH tissues relative to non- hypertrophic ligamentum flavum (LFN) tissues. When SIRT6 was overexpressed in these LFH cells, this was associated with significant increases in telomerase activity and a significant reduction in fibrosis-related protein expression. These effects were reversed, however, when telomerase activity was inactivated by hTERT knockdown in these same cells. SIRT6 overexpression was further found to reduce the frequency of senescence-associated β-galactosidase (SA-β-Gal)-positive LFH cells and to decrease p16, MMP3, and L1 mRNA levels and telomere dysfunction-induced foci (TIFs) in LFH cells. In contrast, hTERT knockdown-induced telomerase inactivation eliminated these SIRT6-dependent effects. Overall, our results indicate that SIRT6 functions as a key protective factor that prevents cellular senescence and telomere dysfunction in ligamentum flavum cells, with this effect being at least partially attributable to SIRT6-dependent telomerase activation.
腰椎管狭窄症（LSS）是一种与年龄相关的纤维化、弹性蛋白与胶原蛋白比例降低以及黄韧带肥厚的病症。本研究旨在评估 SIRT6 与腰椎管狭窄症患者黄韧带肥厚（LFH）细胞中端粒酶活性之间的关系。我们观察到，与非肥厚性黄韧带（LFN）组织相比，LFH 组织中的 SIRT6、TPP1 和 POT1 蛋白水平显著降低，端粒酶逆转录酶（TERT）水平和端粒酶活性显著增加。当在这些 LFH 细胞中过表达 SIRT6 时，与端粒酶活性显著增加和纤维化相关蛋白表达显著减少相关。然而，当通过 hTERT 敲低使这些相同的细胞中端粒酶活性失活时，这些作用被逆转。SIRT6 的过表达还进一步发现减少了衰老相关β-半乳糖苷酶（SA-β-Gal）阳性 LFH 细胞的频率，并降低了 p16、MMP3 和 L1 mRNA 水平以及 LFH 细胞中端粒功能障碍诱导的焦点（TIFs）。相比之下，hTERT 敲低诱导的端粒酶失活消除了这些 SIRT6 依赖性效应。总的来说，我们的结果表明，SIRT6 作为一种关键的保护因子，可防止黄韧带细胞的细胞衰老和端粒功能障碍，其作用至少部分归因于 SIRT6 依赖性端粒酶激活。
