Comparative single‐cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea

IF 8 1区医学 Q1 CELL BIOLOGY

Aging Cell Pub Date : 2024-09-10 DOI:10.1111/acel.14319

Yuhua Xiao, Xu Chen, Zheyao Chen, Wangxuan Dai, Xing Hu, Shuyao Zhang, Jiawei Zhong, Jia Chen, Xu Liu, Lingyi Liang, Youjin Hu

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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.

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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

活性氧（ROS）和氧化应激会加速细胞衰老，但它们对不同组织的影响各不相同。角膜以其强大的抗氧化防御系统而闻名，对癌症等与衰老有关的疾病有较强的抵抗力。然而，角膜在衰老过程中维持 ROS 平衡的确切机制仍不清楚。通过对年轻和老年非人灵长类动物的角膜和其他组织进行单细胞转录组比较分析，我们发现在衰老过程中，ZNF281编码转录组程序在角膜中被特异性激活。进一步研究发现，ZNF281 与 FOXO3 形成了一个正反馈回路，可感知 ROS 水平的升高，并可能通过调节线粒体呼吸链和超氧化物歧化酶 (SOD) 的表达来减轻其影响。重要的是，我们观察到在间充质干细胞中过表达 ZNF281 可防止细胞衰老。总之，这些发现为了解组织特异性衰老和开发针对 ROS 损伤的新疗法提供了可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aging Cell Biochemistry, 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) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) 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.