A comprehensive single-cell atlas of three centenarian cohorts unveils unique natural killer cell signatures and enhanced mutual interactions among peripheral immune cells.
{"title":"A comprehensive single-cell atlas of three centenarian cohorts unveils unique natural killer cell signatures and enhanced mutual interactions among peripheral immune cells.","authors":"Bin Wang, Zehao Zhang, Qing Ouyang, Min Zhang, Mingda Duan, Hongyan Hu, Qingtao Zhang, Xinye Jin, Jie Zhang, Qing Luo, Ding Sun, Hao Li, Zeyu Qu, Xiangmei Chen, Zhifeng Gu, Yizhi Chen","doi":"10.1016/j.ebiom.2025.105922","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Centenarians are considered as an optimal population for studying healthy ageing. However, immune features associated with super longevity have only been investigated in a few small studies using a single research method.</p><p><strong>Methods: </strong>In this study, single-cell RNA sequencing (scRNA-seq), mass cytometry, and flow cytometry analysis were used to analyse the immune feature of peripheral blood mononuclear cells (PBMCs) from 17 centenarians (CENs), 9 of their offsprings (COs), and 14 of their offsprings' spouses or neighbours (controls, CTs) from Lingao County of China. scRNA-seq data from the other two cohorts were downloaded from public databases.</p><p><strong>Findings: </strong>Comprehensive analysis of 31 CENs, 17 COs, and 26 CTs from these three cohorts revealed decreased percentages of B cells and CD4<sup>+</sup> T cells and an increased percentage of natural killer (NK) cells in PBMCs from CENs, compared with CTs. Moreover, NK cells from CENs exhibited relatively \"young\" signatures, including cell subset distribution and key membrane receptor expression. Enhanced RUNX3 expression in NK cells was observed in CENs, with reinforced interactions between NK and T cells, which promoted T cell function by modulating MHC-I, CD99 and MIF signalling.</p><p><strong>Interpretation: </strong>CENs exhibit unique immunological features, especially NK cells with young protein expression signatures and immune functions.</p><p><strong>Funding: </strong>This study was funded by the Sanya Science and Technology Innovation Special Project (No. 2022KJCX02), National Natural Science Foundation of China (No. 32141005, 82270769), Specific Research Fund of the Innovation Platform for Academicians of Hainan Province, and National Key Research and Development Program of China (Nos. 2022YFC3602900, 2022YFC3602902, 2022YFC3602903).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105922"},"PeriodicalIF":10.8000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2025.105922","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Centenarians are considered as an optimal population for studying healthy ageing. However, immune features associated with super longevity have only been investigated in a few small studies using a single research method.
Methods: In this study, single-cell RNA sequencing (scRNA-seq), mass cytometry, and flow cytometry analysis were used to analyse the immune feature of peripheral blood mononuclear cells (PBMCs) from 17 centenarians (CENs), 9 of their offsprings (COs), and 14 of their offsprings' spouses or neighbours (controls, CTs) from Lingao County of China. scRNA-seq data from the other two cohorts were downloaded from public databases.
Findings: Comprehensive analysis of 31 CENs, 17 COs, and 26 CTs from these three cohorts revealed decreased percentages of B cells and CD4+ T cells and an increased percentage of natural killer (NK) cells in PBMCs from CENs, compared with CTs. Moreover, NK cells from CENs exhibited relatively "young" signatures, including cell subset distribution and key membrane receptor expression. Enhanced RUNX3 expression in NK cells was observed in CENs, with reinforced interactions between NK and T cells, which promoted T cell function by modulating MHC-I, CD99 and MIF signalling.
Interpretation: CENs exhibit unique immunological features, especially NK cells with young protein expression signatures and immune functions.
Funding: This study was funded by the Sanya Science and Technology Innovation Special Project (No. 2022KJCX02), National Natural Science Foundation of China (No. 32141005, 82270769), Specific Research Fund of the Innovation Platform for Academicians of Hainan Province, and National Key Research and Development Program of China (Nos. 2022YFC3602900, 2022YFC3602902, 2022YFC3602903).
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍：
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
