Tong Xin, Li Wen-Xing, Liang Jihao, Zheng Yang, Dai Shao-Xing
State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China.
Gene. 2022 Jun 30;829:146501. doi: 10.1016/j.gene.2022.146501. Epub 2022 Apr 19.
Aging is a complex life process that human organs and tissues steadily and continuously decline. Aging has huge heterogeneity, which shows different aging rates among different individuals and in different tissues of the same individual. Many studies of aging are often contradictory and show little common signature. The integrated analysis of these transcriptome datasets will provide an unbiased global view of the aging process. Here, we integrated 8 transcriptome datasets including 757 samples from healthy human blood to study aging from three aspects of gene expression, mutations, and alternative splicing. Surprisingly, we found that transcriptome changes in blood are relatively independent of the chronological age. Further pseudotime analysis revealed two different aging paths (AgingPath1 and AgingPath2) in human blood. The differentially expressed genes (DEGs) along the two paths showed a limited overlap and are enriched in different biological processes. The mutations of DEGs in AgingPath1 are significantly increased in the aging process, while the opposite trend was observed in AgingPath2. Expression quantitative trait loci (eQTL) and splicing quantitative trait loci (sQTL) analysis identified 304 important mutations that can affect both gene expression and alternative splicing during aging. Finally, by comparison between aging and Alzheimer's disease, we identified 37 common DEGs in AgingPath1, AgingPath2 and Alzheimer's disease. These genes may contribute to the shift from aging state to Alzheimer's disease. In summary, this study revealed the two aging paths and the related genes and mutations, which provides a new insight into aging and aging-related disease.
衰老是一个复杂的生命过程，在此过程中人体器官和组织会持续且稳定地衰退。衰老具有巨大的异质性，这表现为不同个体之间以及同一个体的不同组织之间衰老速率不同。许多关于衰老的研究往往相互矛盾，且几乎没有共同特征。对这些转录组数据集进行综合分析将为衰老过程提供一个无偏的全局视角。在此，我们整合了8个转录组数据集，包括来自健康人体血液的757个样本，从基因表达、突变和可变剪接三个方面研究衰老。令人惊讶的是，我们发现血液中的转录组变化相对独立于实际年龄。进一步的伪时间分析揭示了人类血液中的两条不同衰老路径（衰老路径1和衰老路径2）。沿着这两条路径的差异表达基因（DEGs）显示出有限的重叠，并且在不同的生物学过程中富集。衰老路径1中DEGs的突变在衰老过程中显著增加，而在衰老路径2中观察到相反的趋势。表达数量性状位点（eQTL）和剪接数量性状位点（sQTL）分析确定了304个重要突变，这些突变在衰老过程中可同时影响基因表达和可变剪接。最后，通过衰老与阿尔茨海默病之间的比较，我们在衰老路径1、衰老路径2和阿尔茨海默病中鉴定出37个共同的DEGs。这些基因可能促成从衰老状态向阿尔茨海默病的转变。总之，本研究揭示了两条衰老路径以及相关基因和突变，为衰老及衰老相关疾病提供了新的见解。
