Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain‐of‐activity mouse model presents with a premature aging‐like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging, and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75‐week‐old) female C57BL/6 mice with a Cdc42 activity‐specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN‐treated animals displayed a youthful level of the aging‐associated cytokines IL‐1β, IL‐1α, and INFγ in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan.

中文翻译：

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抑制 Cdc42 活性可延长老年雌性 C57BL/6 小鼠的寿命并减少循环炎症细胞因子。

Cdc42 是一种小的 RhoGTPase，在真核细胞中调节多种功能。Cdc42 的活性在老年小鼠的几个组织中显着升高，而 Cdc42 活性获得小鼠模型呈现过早衰老样表型和寿命缩短。这些数据表明 Cdc42 活性升高、衰老和寿命缩短之间存在因果关系。在这里，我们证明了用 Cdc42 活性特异性抑制剂 (CASIN) 连续 4 天对老年（75 周大）雌性 C57BL/6 小鼠进行全身治疗，显着延长了平均和最大寿命。此外，根据血细胞中的 DNA 甲基化水平，老年 CASIN 处理的动物血清中显示出年轻水平的衰老相关细胞因子 IL-1β、IL-1α 和 INFγ，以及显着年轻的表观遗传时钟。总体，