德国莱布尼茨老龄研究所Alessandro Ori小组揭示了多胺通过调节蛋白质稳态维持衰老肠上皮细胞再生。2025年11月24日出版的《自然—细胞生物学》发表了这项成果。

在这里，研究小组描述了5-氟尿嘧啶（一种常用的化疗药物）诱导损伤后的再生时间动态，主题肠组织的蛋白质组学和代谢组学分析以及功能分析。不同年龄小鼠的再生动力学比较显示，损伤后仅在老年上皮细胞中出现蛋白酶抑制应激和多胺水平升高。该研究组发现延迟再生是衰老上皮细胞的内在特征，表现为蛋白质合成减少和泛素化蛋白的积累。体内多胺途径的抑制进一步延缓了老年小鼠的再生，而通过饮食干预或补充多胺来激活该途径足以增强老年肠道的再生能力。他们的发现强调了有希望的上皮目标，旨在解决与衰老相关的组织修复机制下降的干预。Minetti、Omrani等人报告称，延迟的肠道再生是由蛋白质稳态应激引起的，可以通过调节多胺途径动力学来改善。

据悉，衰老抑制了包括人类在内的所有物种肠道上皮的再生潜力，但潜在的主题仍然是未知的。

附：英文原文

Title: Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis

Author: Minetti, Alberto, Omrani, Omid, Brenner, Christiane, Cansiz, Feyza, Imada, Shinya, Rsler, Jonas, Khawaled, Saleh, Allies, Gabriele, Meckelmann, Sven W., Gebert, Nadja, Heinze, Ivonne, Rahnis, Norman, Lu, Jing, Spengler, Katrin, Rasa, Mahdi, Cirri, Emilio, Heller, Regine, Yilmaz, mer, Tasdogan, Alpaslan, Neri, Francesco, Ori, Alessandro

Issue&Volume: 2025-11-24

Abstract: Ageing dampens the regenerative potential of intestinal epithelium across species including humans, yet the underlying causes remain elusive. Here we characterized the temporal dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent, using proteomic and metabolomic profiling of intestinal tissues together with functional assays. The comparison of regeneration dynamics in mice of different ages revealed the emergence of proteostasis stress and increased levels of polyamines following injury exclusively in old epithelia. We show that delayed regeneration is an intrinsic feature of aged epithelial cells that display reduced protein synthesis and the accumulation of ubiquitylated proteins. The inhibition of the polyamine pathway in vivo further delays regeneration in old mice, whereas its activation by dietary intervention or supplementation of polyamines is sufficient to enhance the regenerative capacity of aged intestines. Our findings highlight the promising epithelial targets for interventions aimed at tackling the decline in tissue repair mechanisms associated with ageing. Minetti, Omrani et al. report that delayed intestinal regeneration results from protein homeostasis stress and can be improved by modulation of the polyamine pathway dynamics.

DOI: 10.1038/s41556-025-01804-9

Source: https://www.nature.com/articles/s41556-025-01804-9