老年人的综合深度免疫分析揭示了衰老、性别、吸烟和临床特征的系统水平特征。
Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits.
作者信息
Riemann Lennart, Gutierrez Rodrigo, Odak Ivan, Barros-Martins Joana, Roesner Lennart M, Leon Lara Ximena, Falk Christine, Schulz Thomas F, Hansen Gesine, Werfel Thomas, Förster Reinhold
机构信息
Institute of Immunology, Hannover Medical School, Hannover, Germany; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Institute of Immunology, Hannover Medical School, Hannover, Germany.
出版信息
EBioMedicine. 2025 Feb;112:105558. doi: 10.1016/j.ebiom.2025.105558. Epub 2025 Jan 24.
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.
背景
衰老会增加疾病易感性并降低疫苗反应性，这凸显了更好地了解衰老免疫系统及其临床关联的必要性。然而，由于人类免疫系统的复杂性和显著的个体间差异，对其进行研究仍然具有挑战性。
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名年轻对照者（20 - 40岁）进行了免疫谱分析研究。收集了广泛的人口统计学、临床和实验室数据。使用多色光谱流式细胞术和48种细胞因子血浆检测法进行深度免疫表型分析。数据采用无监督聚类和多数据集整合方法进行分析。
研究结果
我们研究了97种先天性和适应性免疫细胞群体，揭示了老年免疫系统中复杂的年龄和性别相关变化。我们的大样本量使得能够检测到细胞因子和免疫细胞簇中即使是细微的变化。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，肝细胞生长因子和CCL27）。此外，我们确定了与吸烟、肥胖以及骨质疏松症、心力衰竭和痛风等疾病相关的独特免疫特征。
解读
本研究提供了老年个体最全面的免疫谱之一，揭示了与衰老相关的高分辨率免疫变化。我们的研究结果突出了具有临床相关性的免疫特征，增强了我们对衰老相关疾病的理解，并可为未来新治疗方法的研究提供指导，为人类健康和衰老提供转化性见解。
资金来源
德国研究基金会（DFG）根据德国卓越战略 - EXC 2155 - 项目编号390874280提供资金。
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