Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity
Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity
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DOI：
10.1016/j.ebiom.2023.104514
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发表时间：
2023-04-12
期刊：
影响因子：
11.1
通讯作者：
Sebastiani, Paola
中科院分区：
文献类型：
--
作者：
Karagiannis, Tanya T.;Dowrey, Todd W.;Sebastiani, Paola
背景免疫细胞组成和功能的年龄相关变化与多病和死亡率相关。然而，许多百岁老人延缓了衰老相关疾病的发病，这表明精英免疫系统的存在在极高龄时仍然具有高度功能。为了确定衰老和人类极端长寿的免疫特异性模式，我们分析了来自7名百岁老人（平均年龄106岁）的随机样本的外周血单个核细胞（PBMCs）的新单细胞谱和公开的单细胞rna测序（scRNA-seq）数据集，其中包括另外7名百岁老人和52名年龄较小的人（20-89岁）。研究结果证实，随着年龄的增长，淋巴细胞与骨髓细胞的比例以及非细胞毒性细胞与细胞毒性细胞的分布发生了已知的变化，但也发现了百岁老人从CD4+ T细胞到B细胞群的显著变化，这表明他们有暴露于自然和环境免疫原的历史。我们使用流式细胞术对相同的样品进行分析，验证了其中的一些发现。我们的转录分析确定了特殊长寿的细胞类型特征，包括与年龄相关变化的基因（例如，STK17A的表达增加，一种已知参与DNA损伤反应的基因）以及在百岁老人的PBMCs中独特表达的基因（例如，S100A4， S100蛋白家族的一部分，研究与年龄相关的疾病，并与长寿和代谢调节有关）。总的来说，这些数据表明百岁老人拥有独特的、功能强大的免疫系统，这些免疫系统已经成功地适应了历史上的侮辱，从而实现了超常的长寿。
Background Age-related changes in immune cell composition and functionality are associated with multimorbidity and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite immunity that remains highly functional at extreme old age.Methods To identify immune-specific patterns of aging and extreme human longevity, we analyzed novel single cell profiles from the peripheral blood mononuclear cells (PBMCs) of a random sample of 7 centenarians (mean age 106) and publicly available single cell RNA-sequencing (scRNA-seq) datasets that included an additional 7 centenarians as well as 52 people at younger ages (20-89 years). Findings The analysis confirmed known shifts in the ratio of lymphocytes to myeloid cells, and noncytotoxic to cytotoxic cell distributions with aging, but also identified significant shifts from CD4+ T cell to B cell populations in centenarians suggesting a history of exposure to natural and environmental immunogens. We validated several of these findings using flow cytometry analysis of the same samples. Our transcriptional analysis identified cell type signatures specific to exceptional longevity that included genes with age-related changes (e.g., increased expression of STK17A, a gene known to be involved in DNA damage response) as well as genes expressed uniquely in centenarians' PBMCs (e.g., S100A4, part of the S100 protein family studied in age-related disease and connected to longevity and metabolic regulation).Interpretation Collectively, these data suggest that centenarians harbor unique, highly functional immune systems that have successfully adapted to a history of insults allowing for the achievement of exceptional longevity.