Sirtuin family members with lysine deacetylase activity are known to play an important role in anti-aging and longevity. Cellular senescence is one of the hallmarks of aging, and downregulation of sirtuin is reported to induce premature senescence. In this study, we investigated the effects of small-molecule sirtuin inhibitors on cellular senescence. Various small molecules such as tenovin-1 and EX527 were employed for direct sirtuin activity inhibition. U251, SNB-75, and U87MG glioblastoma cells treated with sirtuin inhibitors exhibited phenotypes with nuclear enlargement. Furthermore, treatment of rat primary astrocytes with tenovin-1 also increased the size of the nucleus. The activity of senescence-associated β-galactosidase, a marker of cellular senescence, was induced by tenovin-1 and EX527 treatment in U87MG glioblastoma cells. Consistent with the senescent phenotype, treatment with tenovin-1 increased p53 expression in U87MG cells. This study demonstrated the senescence-inducing effect of sirtuin inhibitors, which are potentially useful tools for senescence research.

中文翻译：

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Sirtuin 抑制剂在胶质母细胞瘤细胞中诱导细胞核扩大和衰老

已知具有赖氨酸脱乙酰酶活性的 Sirtuin 家族成员在抗衰老和长寿方面发挥着重要作用。细胞衰老是衰老的标志之一，据报道，sirtuin 的下调会导致过早衰老。在这项研究中，我们研究了小分子 Sirtuin 抑制剂对细胞衰老的影响。各种小分子如tenovin-1和EX527被用于直接抑制sirtuin活性。用sirtuin 抑制剂处理的U251、SNB-75 和U87MG 胶质母细胞瘤细胞表现出核增大的表型。此外，用tenovin-1处理大鼠原代星形胶质细胞也增加了细胞核的大小。在 U87MG 胶质母细胞瘤细胞中，tenovin-1 和 EX527 处理可诱导衰老相关 β-半乳糖苷酶（细胞衰老的标志物）的活性。与衰老表型一致，tenovin-1 处理增加了 U87MG 细胞中 p53 的表达。该研究证明了sirtuin抑制剂的衰老诱导作用，它们是衰老研究的潜在有用工具。