Arginine metabolism is a biomarker of red blood cell and human aging.

IF 8 1区医学 Q1 CELL BIOLOGY

Aging Cell Pub Date : 2024-10-30 DOI:10.1111/acel.14388

Julie A Reisz, Eric J Earley, Travis Nemkov, Alicia Key, Daniel Stephenson, Gregory R Keele, Monika Dzieciatkowska, Steven L Spitalnik, Eldad A Hod, Steven Kleinman, Nareg H Roubinian, Mark T Gladwin, Kirk C Hansen, Philip J Norris, Michael P Busch, James C Zimring, Gary A Churchill, Grier P Page, Angelo D'Alessandro

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引用次数: 0

Abstract

Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics approaches identified chronological age-related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and were influenced by genetic variation, sex, and body mass index. Integrating multi-omics data and metabolite quantitative trait loci (mQTL) in humans and 525 diversity outbred mice functionally linked metabolism of arginine during RBC storage to increased vesiculation-a hallmark of RBC aging-and lower post-transfusion hemoglobin increments. Thus, arginine metabolism is a biomarker of RBC and organismal aging, suggesting potential new targets for addressing sequelae of aging.

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精氨酸代谢是红细胞和人体衰老的生物标志物。

全球预期寿命的不断延长促使人们对衰老和老年相关疾病的分子机制进行研究。本研究探讨了人类数量最多的宿主细胞--红细胞（RBC）与年龄相关的变化。研究分析了包括健康人和镰状细胞病患者在内的四个队列，以确定红细胞新陈代谢随年龄的变化。研究人员对来自 13757 人的 15,700 多份标本进行了检测，这比以往有关衰老过程中红细胞的研究有了大幅扩展。多组学方法确定了精氨酸通路中与时间年龄相关的变化，在老年人的红细胞中精氨酸利用率增加。这些变化在健康和镰状细胞疾病队列中是一致的，并受遗传变异、性别和体重指数的影响。通过整合人类和 525 种多样性近交系小鼠的多组学数据和代谢物定量性状位点 (mQTL)，在功能上将红细胞储存过程中的精氨酸代谢与囊泡化增加（红细胞老化的标志）和输血后血红蛋白增量降低联系起来。因此，精氨酸代谢是 RBC 和机体衰老的生物标志物，为解决衰老后遗症提出了潜在的新目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.