Senescence-resistant human mesenchymal progenitor cells counter aging in primates

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-06-13 DOI:10.1016/j.cell.2025.05.021

Jinghui Lei, Zijuan Xin, Ning Liu, Taixin Ning, Ying Jing, Yicheng Qiao, Zan He, Mengmeng Jiang, Yuanhan Yang, Zhiyi Zhang, Liyun Zhao, Jingyi Li, Dongliang Lv, Yupeng Yan, Hui Zhang, Lingling Xiao, Baohu Zhang, Haoyan Huang, Shuhui Sun, Fangshuo Zheng, Guang-Hui Liu

{"title":"Senescence-resistant human mesenchymal progenitor cells counter aging in primates","authors":"Jinghui Lei, Zijuan Xin, Ning Liu, Taixin Ning, Ying Jing, Yicheng Qiao, Zan He, Mengmeng Jiang, Yuanhan Yang, Zhiyi Zhang, Liyun Zhao, Jingyi Li, Dongliang Lv, Yupeng Yan, Hui Zhang, Lingling Xiao, Baohu Zhang, Haoyan Huang, Shuhui Sun, Fangshuo Zheng, Guang-Hui Liu","doi":"10.1016/j.cell.2025.05.021","DOIUrl":null,"url":null,"abstract":"Aging is characterized by a deterioration of stem cell function, but the feasibility of replenishing these cells to counteract aging remains poorly defined. Our study addresses this gap by developing senescence (seno)-resistant human mesenchymal progenitor cells (SRCs), genetically fortified to enhance cellular resilience. In a 44-week trial, we intravenously delivered SRCs to aged macaques, noting a systemic reduction in aging indicators, such as cellular senescence, chronic inflammation, and tissue degeneration, without any detected adverse effects. Notably, SRC treatment enhanced brain architecture and cognitive function and alleviated the reproductive system decline. The restorative effects of SRCs are partly attributed to their exosomes, which combat cellular senescence. This study provides initial evidence that genetically modified human mesenchymal progenitors can slow primate aging, highlighting the therapeutic potential of regenerative approaches in combating age-related health decline.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"609 1","pages":""},"PeriodicalIF":45.5000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2025.05.021","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aging is characterized by a deterioration of stem cell function, but the feasibility of replenishing these cells to counteract aging remains poorly defined. Our study addresses this gap by developing senescence (seno)-resistant human mesenchymal progenitor cells (SRCs), genetically fortified to enhance cellular resilience. In a 44-week trial, we intravenously delivered SRCs to aged macaques, noting a systemic reduction in aging indicators, such as cellular senescence, chronic inflammation, and tissue degeneration, without any detected adverse effects. Notably, SRC treatment enhanced brain architecture and cognitive function and alleviated the reproductive system decline. The restorative effects of SRCs are partly attributed to their exosomes, which combat cellular senescence. This study provides initial evidence that genetically modified human mesenchymal progenitors can slow primate aging, highlighting the therapeutic potential of regenerative approaches in combating age-related health decline.

Abstract Image

查看原文本刊更多论文

抗衰老的人类间充质祖细胞对抗灵长类动物的衰老

衰老的特征是干细胞功能的退化，但补充这些细胞以对抗衰老的可行性仍不明确。我们的研究通过开发抗衰老（seno）的人间充质祖细胞（src）来解决这一差距，基因强化以增强细胞弹性。在一项为期44周的试验中，我们向老年猕猴静脉注射了src，发现衰老指标（如细胞衰老、慢性炎症和组织变性）的系统性减少，没有发现任何不良反应。值得注意的是，SRC治疗增强了大脑结构和认知功能，缓解了生殖系统的衰退。src的恢复作用部分归因于其抗细胞衰老的外泌体。这项研究提供了初步证据，证明转基因人类间充质祖细胞可以减缓灵长类动物的衰老，突出了再生方法在对抗与年龄相关的健康衰退方面的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.