美国麻省理工学院和哈佛大学博德研究所斯坦利精神病学研究中心Paola Arlotta等合作的最新研究，发现人类大脑类器官记录了多年的时间流逝。2026年8月19日，国际知名学术期刊《自然》发表了这一成果。

人类大脑的发育和成熟跨越了生命中近二十年的超长时期，这一过程极为漫长。控制人类出生后大脑发育中物种特异性方面的进程，难以在动物模型中研究。虽然人脑类器官提供了一种有前景的体外模型，但迄今为止它们主要被证明模拟大脑发育的早期阶段。在此，研究人员将人脑类器官在培养中维持了5年，优化了生长条件，将兴奋性神经元的存活时间延长至超越此前的极限。利用源于内源性人脑的成熟相关模块，研究人员证明，脑类器官在数年的培养过程中以细胞类型特异性的方式在转录水平上老化。全基因组甲基化谱分析显示，类器官的预测表观遗传年龄与体外培养时间精确相关，并与体内表观遗传老化平行。

值得注意的是，研究人员发现，在通过混合不同年龄的神经祖细胞生成的嵌合类器官中，年老祖细胞快速产生晚期神经元命运，跳过了早期神经元后代的产生，这表明在类器官中老化的祖细胞保留了体外培养时间的记忆。数据表明，人脑类器官可以在培养中继续成熟并记录数年的时间流逝。

附：英文原文

Title: Human brain organoids record the passage of time over multiple years

Author: Faravelli, Irene, Antn-Bolaos, Noelia, Wei, Anqi, Faits, Tyler, Kumar, Abhishek Sampath, Andreadis, Sophia, Kastli, Rahel, Crespo, Marta Montero, Steiger, Mara, Leible, Daniel, Zhang, Elizabeth, An, Bobae, Meirovitch, Yaron, Silwal, Sayara, Yang, Sung Min, Kovacsovics, Alexander, Adiconis, Xian, Kretzmer, Helene, Levin, Joshua Z., Boyden, Edward S., Lichtman, Jeff, Regev, Aviv, Meissner, Alexander, Arlotta, Paola

Issue&Volume: 2026-08-19

Abstract: The human brain develops and matures over an exceptionally prolonged period of time that spans nearly two decades of life. Processes that govern species-specific aspects of human postnatal brain development are difficult to study in animal models1. While human brain organoids offer a promising in vitro model, they have thus far been shown to largely mimic early stages of brain development. Here we develop human brain organoids for 5years in culture, optimizing growth conditions to extend excitatory neuron viability beyond previous limits. Using maturation-associated modules derived from endogenous human brain, we show that brain organoids transcriptionally age with cell type specificity over years in culture. Whole-genome methylation profiling reveals that the predicted epigenomic age of organoids correlates precisely with time spent in vitro, and parallels epigenomic ageing in vivo. Notably, we show that in chimeric organoids generated by mixing neural progenitors of different ages, old progenitors rapidly produce late neuronal fates, skipping the production of earlier neuronal progeny, therefore showing that progenitors that age in organoids retain a memory of the time spent in vitro. The data indicate that human brain organoids can continue to mature and record the passage of time over many years in culture.

DOI: 10.1038/s41586-026-10877-x

Source: https://www.nature.com/articles/s41586-026-10877-x