Intestinal epithelial cells are critical for gastrointestinal homeostasis. However, their function declines during aging. The aging-related loss of organ performance is largely driven by the increase in senescent cells. To date, the hallmarks and molecular mechanisms related to cellular senescence are not fully understood. Microtubules control epithelial functions, and we identified microtubule stabilization as a phenotypic marker of senescent intestinal epithelial cells. The senescence inducer determined the pathway to microtubule stabilization. Specifically, enhanced microtubule stability was associated with α-tubulin hyperacetylation or increased abundance of the microtubule-binding protein tau. We show further that overexpression of MAPT, which encodes tau, augmented microtubule stability in intestinal epithelial cells. Notably, pharmacological microtubule stabilization was sufficient to induce cellular senescence. Taken together, this study provides new insights into the molecular mechanisms that control epithelial cell homeostasis. Our results support the concept that microtubule stability serves as a critical cue to trigger intestinal epithelial cell senescence.

肠上皮细胞对胃肠道稳态至关重要。然而，它们的功能会随着衰老而下降。与衰老相关的器官功能丧失主要是由衰老细胞的增加引起的。迄今为止，与细胞衰老相关的标志和分子机制尚不完全清楚。微管控制上皮功能，我们将微管稳定性确定为衰老肠上皮细胞的表型标记。衰老诱导剂决定了微管稳定化的途径。具体而言，增强的微管稳定性与 α-微管蛋白过度乙酰化或微管结合蛋白 tau 的丰度增加有关。我们进一步表明MAPT的过表达，它编码 tau，增强肠上皮细胞中的微管稳定性。值得注意的是，药理学微管稳定足以诱导细胞衰老。总之，这项研究为控制上皮细胞稳态的分子机制提供了新的见解。我们的结果支持微管稳定性作为触发肠上皮细胞衰老的关键线索的概念。