Integrating bulk and single-cell transcriptomics to elucidate the role and potential mechanisms of autophagy in aging tissue.

IF 6.6 2区医学 Q1 Medicine Cellular Oncology Pub Date : 2024-10-16 DOI:10.1007/s13402-024-00996-w

Zhenhua Zhu, Linsen Li, Youqiong Ye, Qing Zhong

{"title":"Integrating bulk and single-cell transcriptomics to elucidate the role and potential mechanisms of autophagy in aging tissue.","authors":"Zhenhua Zhu, Linsen Li, Youqiong Ye, Qing Zhong","doi":"10.1007/s13402-024-00996-w","DOIUrl":null,"url":null,"abstract":"Purpose: Autophagy is frequently observed in tissues during the aging process, yet the tissues most strongly correlated with autophagy during aging and the underlying regulatory mechanisms remain inadequately understood. The purpose of this study is to identify the tissues with the highest correlation between autophagy and aging, and to explore the functions and mechanisms of autophagy in the aging tissue microenvironment.Methods: Integrated bulk RNA-seq from over 7000 normal tissue samples, single-cell sequencing data from blood samples of different ages, more than 2000 acute myeloid leukemia (AML) bulk RNA-seq, and multiple sets of AML single-cell data. The datasets were analysed using various bioinformatic approaches.Results: Blood tissue exhibited the highest positive correlation between autophagy and aging among healthy tissues. Single-cell resolution analysis revealed that in aged blood, classical monocytes (C. monocytes) are most closely associated with elevated autophagy levels. Increased autophagy in these monocytes correlated with a higher proportion of C. monocytes, with hypoxia identified as a crucial contributing factor. In AML, a representative myeloid blood disease, enhanced autophagy was accompanied by an increased proportionof C. monocytes. High autophagy levels in monocytes are associated with pro-inflammatory gene upregulation and Reactive Oxygen Species (ROS) accumulation, contributing to tissue aging.Conclusion: This study revealed that autophagy is most strongly correlated with aging in blood tissue. Enhanced autophagy levels in C. monocytes demonstrate a positive correlation with increased secretion of pro-inflammatory factors and elevated production of ROS, which may contribute to a more rapid aging process. This discovery underscores the critical role of autophagy in blood aging and suggests potential therapeutic targets to mitigate aging-related health issues.","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13402-024-00996-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: Autophagy is frequently observed in tissues during the aging process, yet the tissues most strongly correlated with autophagy during aging and the underlying regulatory mechanisms remain inadequately understood. The purpose of this study is to identify the tissues with the highest correlation between autophagy and aging, and to explore the functions and mechanisms of autophagy in the aging tissue microenvironment.

Methods: Integrated bulk RNA-seq from over 7000 normal tissue samples, single-cell sequencing data from blood samples of different ages, more than 2000 acute myeloid leukemia (AML) bulk RNA-seq, and multiple sets of AML single-cell data. The datasets were analysed using various bioinformatic approaches.

Results: Blood tissue exhibited the highest positive correlation between autophagy and aging among healthy tissues. Single-cell resolution analysis revealed that in aged blood, classical monocytes (C. monocytes) are most closely associated with elevated autophagy levels. Increased autophagy in these monocytes correlated with a higher proportion of C. monocytes, with hypoxia identified as a crucial contributing factor. In AML, a representative myeloid blood disease, enhanced autophagy was accompanied by an increased proportionof C. monocytes. High autophagy levels in monocytes are associated with pro-inflammatory gene upregulation and Reactive Oxygen Species (ROS) accumulation, contributing to tissue aging.

Conclusion: This study revealed that autophagy is most strongly correlated with aging in blood tissue. Enhanced autophagy levels in C. monocytes demonstrate a positive correlation with increased secretion of pro-inflammatory factors and elevated production of ROS, which may contribute to a more rapid aging process. This discovery underscores the critical role of autophagy in blood aging and suggests potential therapeutic targets to mitigate aging-related health issues.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

整合体细胞和单细胞转录组学，阐明自噬在衰老组织中的作用和潜在机制。

目的：自噬在衰老过程中经常在组织中被观察到，然而衰老过程中与自噬相关性最强的组织及其潜在的调控机制仍未被充分了解。本研究旨在确定自噬与衰老相关性最高的组织，并探索自噬在衰老组织微环境中的功能和机制：整合了7000多份正常组织样本的大量RNA-seq数据、不同年龄段血液样本的单细胞测序数据、2000多份急性髓性白血病（AML）的大量RNA-seq数据以及多组AML单细胞数据。这些数据集采用了各种生物信息学方法进行分析：结果：在健康组织中，血液组织显示出自噬与衰老之间最高的正相关性。单细胞分辨率分析显示，在衰老的血液中，经典单核细胞（C. monocytes）与自噬水平升高的关系最为密切。这些单核细胞自噬水平的升高与 C. 单核细胞比例的升高有关，而缺氧被认为是一个重要的促成因素。在具有代表性的骨髓性血液疾病急性髓性白血病中，自噬的增强伴随着C. 单核细胞比例的增加。单核细胞的高自噬水平与促炎基因上调和活性氧（ROS）积累有关，从而导致组织老化：这项研究表明，自噬与血液组织的衰老关系最为密切。C.单核细胞自噬水平的提高与促炎因子分泌的增加和 ROS 生成的增加呈正相关，这可能会导致更快的衰老过程。这一发现强调了自噬在血液衰老中的关键作用，并提出了缓解衰老相关健康问题的潜在治疗目标。

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分钟内获得全文去求助

来源期刊

Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

10.40

自引率

1.50%

发文量

审稿时长

16 weeks

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.