In our recent transcriptomic meta-analysis, we used random forest machine learning to accurately predict age in human blood, bone, brain, heart, and retina tissues given gene inputs. Although each tissue-specific model utilized a unique number of genes for age prediction, we found that the following six genes were prioritized in all five tissues: CHI3L2, CIDEC, FCGR3A, RPS4Y1, SLC11A1, and VTCN1. Since being selected for age prediction in multiple tissues is unique, we decided to explore these pan-tissue clock genes in greater detail. In the present study, we began by performing over-representation and network topology-based enrichment analyses in the Gene Ontology Biological Process database. These analyses revealed that the immunological terms “response to protozoan,” “immune response,” and “positive regulation of immune system process” were significantly enriched by these clock inputs. Expression analyses in mouse and human tissues identified that these inputs are frequently upregulated or downregulated with age. A detailed literature search showed that all six genes had noteworthy connections to age-related disease. For example, mice deficient in Cidec are protected against various metabolic defects, while suppressing VTCN1 inhibits age-related cancers in mouse models. Using a large multitissue transcriptomic dataset, we additionally generate a novel, minimalistic aging clock that can predict human age using just these six genes as inputs. Taken all together, these six genes are connected to diverse aspects of aging.

中文翻译：

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与免疫系统和年龄相关疾病有密切联系的泛组织衰老时钟基因

在我们最近的转录组元分析中，我们使用随机森林机器学习来准确预测给定基因输入的人类血液、骨骼、大脑、心脏和视网膜组织的年龄。尽管每个组织特异性模型都使用了独特数量的基因进行年龄预测，但我们发现以下 6 个基因在所有 5 个组织中都被优先考虑：CHI3L2、CIDEC、FCGR3A、RPS4Y1、SLC11A1和VTCN1. 由于在多个组织中被选择用于年龄预测是独一无二的，我们决定更详细地探索这些泛组织时钟基因。在本研究中，我们首先在 Gene Ontology Biological Process 数据库中执行过度表征和基于网络拓扑的富集分析。这些分析表明，这些时钟输入显着丰富了免疫学术语“对原生动物的反应”、“免疫反应”和“免疫系统过程的正调节”。小鼠和人体组织中的表达分析表明，这些输入经常随着年龄的增长而上调或下调。详细的文献搜索表明，所有六个基因都与年龄相关疾病有显着联系。例如，缺乏Cidec 的小鼠可防止各种代谢缺陷，同时抑制 VTCN1 可抑制小鼠模型中与年龄相关的癌症。使用大型多组织转录组数据集，我们还生成了一个新颖的、简约的衰老时钟，可以仅使用这六个基因作为输入来预测人类年龄。总之，这六个基因与衰老的各个方面有关。