{"title":"对衰老灵长类动物各组织的单细胞转录组比较分析表明,ZNF281 的特异性自体激活可减轻角膜的氧化应激反应","authors":"Yuhua Xiao, Xu Chen, Zheyao Chen, Wangxuan Dai, Xing Hu, Shuyao Zhang, Jiawei Zhong, Jia Chen, Xu Liu, Lingyi Liang, Youjin Hu","doi":"10.1111/acel.14319","DOIUrl":null,"url":null,"abstract":"Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age‐related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single‐cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue‐specific aging and developing new therapies targeting ROS damage.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparative single‐cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea\",\"authors\":\"Yuhua Xiao, Xu Chen, Zheyao Chen, Wangxuan Dai, Xing Hu, Shuyao Zhang, Jiawei Zhong, Jia Chen, Xu Liu, Lingyi Liang, Youjin Hu\",\"doi\":\"10.1111/acel.14319\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age‐related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single‐cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue‐specific aging and developing new therapies targeting ROS damage.\",\"PeriodicalId\":119,\"journal\":{\"name\":\"Aging Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.0000,\"publicationDate\":\"2024-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1111/acel.14319\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/acel.14319","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Comparative single‐cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea
Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age‐related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single‐cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue‐specific aging and developing new therapies targeting ROS damage.
Aging CellBiochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍:
Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health.
The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include:
Academic Search (EBSCO Publishing)
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Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.