Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits.

IF 10.8 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2025-02-01 Epub Date: 2025-01-24 DOI:10.1016/j.ebiom.2025.105558
Lennart Riemann, Rodrigo Gutierrez, Ivan Odak, Joana Barros-Martins, Lennart M Roesner, Ximena Leon Lara, Christine Falk, Thomas F Schulz, Gesine Hansen, Thomas Werfel, Reinhold Förster
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Abstract

Background: Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inter-individual variability.

Methods: We conducted an immune profiling study of 550 elderly participants (≥60 years) and 100 young controls (20-40 years) from the RESIST Senior Individuals (SI) cohort. Extensive demographic, clinical, and laboratory data were collected. Multi-color spectral flow cytometry and 48-plex plasma cytokine assays were used for deep immune phenotyping. Data were analyzed using unsupervised clustering and multi-dataset integration approaches.

Findings: We studied 97 innate and adaptive immune cell populations, revealing intricate age- and sex-related changes in the elderly immune system. Our large sample size allowed detection of even subtle changes in cytokines and immune cell clusters. Integrative analysis combining clinical, laboratory, and immunological data revealed systems-level aging signatures, including shifts in specific immune cell subpopulations and cytokine concentrations (e.g., HGF and CCL27). Additionally, we identified unique immune signatures associated with smoking, obesity, and diseases such as osteoporosis, heart failure, and gout.

Interpretation: This study provides one of the most comprehensive immune profiles of elderly individuals, uncovering high-resolution immune changes associated with aging. Our findings highlight clinically relevant immune signatures that enhance our understanding of aging-related diseases and could guide future research into new treatments, offering translational insights into human health and aging.

Funding: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy-EXC 2155-project number 390874280.

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老年人的综合深度免疫分析揭示了年龄、性别、吸烟和临床特征的系统水平特征。
背景:衰老增加疾病易感性,降低疫苗反应性,强调需要更好地了解衰老免疫系统及其临床关联。然而,由于人类免疫系统的复杂性和显著的个体间变异性,研究人类免疫系统仍然具有挑战性。方法:我们对来自RESIST老年个体(SI)队列的550名老年参与者(≥60岁)和100名年轻对照(20-40岁)进行了免疫分析研究。收集了广泛的人口统计、临床和实验室数据。采用多色光谱流式细胞术和48-plex血浆细胞因子测定进行深度免疫表型分析。数据分析采用无监督聚类和多数据集集成方法。研究结果:我们研究了97个先天和适应性免疫细胞群,揭示了老年人免疫系统中复杂的年龄和性别相关变化。我们的大样本量可以检测到细胞因子和免疫细胞簇的细微变化。结合临床、实验室和免疫学数据的综合分析揭示了系统水平的衰老特征,包括特定免疫细胞亚群和细胞因子浓度的变化(例如,HGF和CCL27)。此外,我们还发现了与吸烟、肥胖和骨质疏松、心力衰竭和痛风等疾病相关的独特免疫特征。解释:这项研究提供了老年人最全面的免疫概况之一,揭示了与衰老相关的高分辨率免疫变化。我们的发现强调了临床相关的免疫特征,增强了我们对衰老相关疾病的理解,并可以指导未来研究新的治疗方法,为人类健康和衰老提供转化性见解。资助:德国卓越战略项目exc 2155,项目编号390874280。
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来源期刊
EBioMedicine
EBioMedicine Biochemistry, 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.
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