Qin Peizhong, Wang Qi, Wu You, You Qiqi, Li Mingyu, Guo Zheng
Department of Medical Genetics, School of Basic Medicine, Institute for Brain Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nat Commun. 2025 Jul 22;16(1):6734. doi: 10.1038/s41467-025-62043-y.
Improving gut health by altering the activity of intestinal stem cells is thought to have the potential to reverse aging. The aged Drosophila midgut undergoes hyperplasia and barrier dysfunction. However, it is still unclear how to limit hyperplasia to extend lifespan. Here, we show that early midgut injury prevents the abrupt onset of aging hyperplasia and extends lifespan in flies. Daily transcriptome profiling and lineage tracing analysis show that the abrupt onset of aging hyperplasia is due to the collective turnover of developmentally generated "old" enterocytes (ECs). Early injury introduces new ECs into the old EC population, forming the epithelial age mosaic. Age mosaic avoids collective EC turnover and facilitates septate junction formation, thereby improving the epithelial barrier and extending lifespan. Furthermore, we found that intermittent time-restricted feeding benefits health by creating an EC age mosaic. Our findings suggest that age mosaic may become a therapeutic approach to reverse aging.
通过改变肠道干细胞的活性来改善肠道健康被认为具有逆转衰老的潜力。衰老的果蝇中肠会发生增生和屏障功能障碍。然而，目前仍不清楚如何限制增生以延长寿命。在此，我们表明早期中肠损伤可防止衰老增生的突然发生，并延长果蝇的寿命。每日转录组分析和谱系追踪分析表明，衰老增生的突然发生是由于发育产生的“老”肠上皮细胞（ECs）的集体更新。早期损伤将新的ECs引入到老的ECs群体中，形成上皮年龄镶嵌体。年龄镶嵌体避免了ECs的集体更新，并促进了隔膜连接的形成，从而改善上皮屏障并延长寿命。此外，我们发现间歇性限时进食通过创造EC年龄镶嵌体而有益于健康。我们的研究结果表明，年龄镶嵌体可能成为一种逆转衰老的治疗方法。
