血浆细胞外囊泡携带免疫系统相关肽,预测人类寿命

IF 5.3 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Xin Zhang, Sisi Ma, Syeda Iffat Naz, Erik J. Soderblom, Constantin Aliferis, Virginia Byers Kraus
{"title":"血浆细胞外囊泡携带免疫系统相关肽,预测人类寿命","authors":"Xin Zhang, Sisi Ma, Syeda Iffat Naz, Erik J. Soderblom, Constantin Aliferis, Virginia Byers Kraus","doi":"10.1007/s11357-024-01454-z","DOIUrl":null,"url":null,"abstract":"<p>Extracellular vesicles (EVs) play crucial roles in aging. In this National Institutes on Aging-funded study, we sought to identify circulating extracellular vesicle (EV) biomarkers indicative of longevity. The plasma EV proteome of 48 older adults (mean age 77.2 ± 1.7 years [range 72–80]; 50% female, 50% Black, 50% &lt; 2-year survival, 50% ≥ 10-year survival) was analyzed by high-resolution mass spectrometry and flow cytometry. The ability of EV peptides to predict longevity was evaluated in discovery (<i>n</i> = 32) and validation (<i>n</i> = 16) datasets with areas under receiver operating characteristic curves (AUCs). Longevity-associated large EV (LEV) plasma subpopulations were mainly related to immune cells (HLA-ABC<sup>+</sup>, CD9<sup>+</sup>, and CD31<sup>+</sup>) and muscle cells (MCAD<sup>+</sup> and RyR2<sup>+</sup>). Of 7960 identified plasma EV peptides (519 proteins), 46.4% were related to the immune system and 10.1% to muscle. Compared with short-lived older adults, 756 EV peptides (131 proteins) had a higher abundance, and 130 EV peptides (78 proteins) had a lower abundance in long-lived adults. Among longevity-associated peptides, 437 (58 proteins) were immune system related, and 12 (2 proteins) were muscle related. Using just three to five plasma EV peptides (mainly complement components C2-C6), we achieved high predictive accuracy for longevity (AUC range 0.91–1 in a hold-out validation dataset). Our findings suggest that immune cells produce longevity-associated plasma EVs and elucidate fundamental mechanisms regulating aging and longevity. EV longevity predictors suggest there may be merit in targeting complement pathways to extend lifespan, for instance, with any one of the multiple complement inhibitors currently available or in clinical development.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"31 1","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plasma extracellular vesicles carry immune system-related peptides that predict human longevity\",\"authors\":\"Xin Zhang, Sisi Ma, Syeda Iffat Naz, Erik J. Soderblom, Constantin Aliferis, Virginia Byers Kraus\",\"doi\":\"10.1007/s11357-024-01454-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Extracellular vesicles (EVs) play crucial roles in aging. In this National Institutes on Aging-funded study, we sought to identify circulating extracellular vesicle (EV) biomarkers indicative of longevity. The plasma EV proteome of 48 older adults (mean age 77.2 ± 1.7 years [range 72–80]; 50% female, 50% Black, 50% &lt; 2-year survival, 50% ≥ 10-year survival) was analyzed by high-resolution mass spectrometry and flow cytometry. The ability of EV peptides to predict longevity was evaluated in discovery (<i>n</i> = 32) and validation (<i>n</i> = 16) datasets with areas under receiver operating characteristic curves (AUCs). Longevity-associated large EV (LEV) plasma subpopulations were mainly related to immune cells (HLA-ABC<sup>+</sup>, CD9<sup>+</sup>, and CD31<sup>+</sup>) and muscle cells (MCAD<sup>+</sup> and RyR2<sup>+</sup>). Of 7960 identified plasma EV peptides (519 proteins), 46.4% were related to the immune system and 10.1% to muscle. Compared with short-lived older adults, 756 EV peptides (131 proteins) had a higher abundance, and 130 EV peptides (78 proteins) had a lower abundance in long-lived adults. Among longevity-associated peptides, 437 (58 proteins) were immune system related, and 12 (2 proteins) were muscle related. Using just three to five plasma EV peptides (mainly complement components C2-C6), we achieved high predictive accuracy for longevity (AUC range 0.91–1 in a hold-out validation dataset). Our findings suggest that immune cells produce longevity-associated plasma EVs and elucidate fundamental mechanisms regulating aging and longevity. EV longevity predictors suggest there may be merit in targeting complement pathways to extend lifespan, for instance, with any one of the multiple complement inhibitors currently available or in clinical development.</p>\",\"PeriodicalId\":12730,\"journal\":{\"name\":\"GeroScience\",\"volume\":\"31 1\",\"pages\":\"\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-12-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"GeroScience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11357-024-01454-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"GeroScience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11357-024-01454-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

细胞外囊泡(EVs)在衰老中起着至关重要的作用。在这项由美国国家老龄研究所资助的研究中,我们试图确定指示寿命的循环细胞外囊泡(EV)生物标志物。48例老年人(平均77.2±1.7岁[72 ~ 80岁])血浆EV蛋白质组;50%为女性,50%为黑人,50%为2年生存率,50%≥10年生存率),采用高分辨率质谱法和流式细胞术进行分析。在发现(n = 32)和验证(n = 16)数据集中评估EV肽预测寿命的能力,这些数据集具有受试者工作特征曲线(auc)下的面积。长寿相关的大EV (LEV)血浆亚群主要与免疫细胞(HLA-ABC+、CD9+和CD31+)和肌肉细胞(MCAD+和RyR2+)有关。在已鉴定的7960种血浆EV肽(519种蛋白)中,46.4%与免疫系统有关,10.1%与肌肉有关。与寿命较短的老年人相比,756个EV肽(131种蛋白质)的丰度较高,而130个EV肽(78种蛋白质)的丰度较低。在长寿相关肽中,437(58个蛋白)与免疫系统相关,12(2个蛋白)与肌肉相关。仅使用三到五种血浆EV肽(主要是补体成分C2-C6),我们就实现了对寿命的高预测精度(在保留验证数据集中的AUC范围为0.91-1)。我们的研究结果表明,免疫细胞产生与寿命相关的血浆EVs,并阐明了调节衰老和寿命的基本机制。EV寿命预测表明,针对补体途径延长寿命可能有价值,例如,目前可用的多种补体抑制剂中的任何一种或在临床开发中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma extracellular vesicles carry immune system-related peptides that predict human longevity

Extracellular vesicles (EVs) play crucial roles in aging. In this National Institutes on Aging-funded study, we sought to identify circulating extracellular vesicle (EV) biomarkers indicative of longevity. The plasma EV proteome of 48 older adults (mean age 77.2 ± 1.7 years [range 72–80]; 50% female, 50% Black, 50% < 2-year survival, 50% ≥ 10-year survival) was analyzed by high-resolution mass spectrometry and flow cytometry. The ability of EV peptides to predict longevity was evaluated in discovery (n = 32) and validation (n = 16) datasets with areas under receiver operating characteristic curves (AUCs). Longevity-associated large EV (LEV) plasma subpopulations were mainly related to immune cells (HLA-ABC+, CD9+, and CD31+) and muscle cells (MCAD+ and RyR2+). Of 7960 identified plasma EV peptides (519 proteins), 46.4% were related to the immune system and 10.1% to muscle. Compared with short-lived older adults, 756 EV peptides (131 proteins) had a higher abundance, and 130 EV peptides (78 proteins) had a lower abundance in long-lived adults. Among longevity-associated peptides, 437 (58 proteins) were immune system related, and 12 (2 proteins) were muscle related. Using just three to five plasma EV peptides (mainly complement components C2-C6), we achieved high predictive accuracy for longevity (AUC range 0.91–1 in a hold-out validation dataset). Our findings suggest that immune cells produce longevity-associated plasma EVs and elucidate fundamental mechanisms regulating aging and longevity. EV longevity predictors suggest there may be merit in targeting complement pathways to extend lifespan, for instance, with any one of the multiple complement inhibitors currently available or in clinical development.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
GeroScience
GeroScience Medicine-Complementary and Alternative Medicine
CiteScore
10.50
自引率
5.40%
发文量
182
期刊介绍: GeroScience is a bi-monthly, international, peer-reviewed journal that publishes articles related to research in the biology of aging and research on biomedical applications that impact aging. The scope of articles to be considered include evolutionary biology, biophysics, genetics, genomics, proteomics, molecular biology, cell biology, biochemistry, endocrinology, immunology, physiology, pharmacology, neuroscience, and psychology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信