小柯机器人

衰老标志着特定器官的时间特征
2020-07-16 17:02

美国斯坦福大学Tony Wyss-Coray和Stephen R. Quake研究组合作取得一项新突破。他们的最新研究提出衰老标志着特定器官的时间特征。相关论文发表在2020年7月15日出版的《自然》杂志上。

他们在小家鼠的整个寿命中对10个年龄段的17个器官和血浆蛋白质组学进行了大体积RNA测序,并将这些发现与共同测序的Tabula Muris Senis(或“ 小鼠衰老细胞图集”)的数据(源自原始Tabula)整合。他们揭示了衰老过程中基因表达的线性和非线性变化,相关基因聚集在具有相同生物学功能(包括细胞外基质调节,未折叠蛋白结合,线粒体功能以及炎症和免疫反应)的一致轨迹组中。

值得注意的是,这些基因集在整个组织中表现出相似的表达,只是表达的幅度和年龄不同。免疫细胞的广泛激活特别明显,并且首先在中年时期白色脂肪库中被检测到。单细胞RNA测序证实了脂肪组织(包括表达免疫球蛋白J的浆细胞)中T细胞和B细胞的积累,这些脂肪也同时在多种器官中累积。最后,他们显示了不同组织中的基因表达变化如何与血浆中相应的蛋白质水平高度相关,从而潜在地促进了体循环的衰老。这些数据一起证明了相似的器官间和器官内异步的衰老进程,为跟踪衰老的健康衰退的系统性来源提供了基础。

据介绍,衰老是全球疾病和死亡的最大原因,了解相关过程可以极大地改善生活质量。尽管已经确定了衰老损害的主要类别,例如改变的细胞间通讯,蛋白稳态丧失和线粒体功能受到损害,但这些有害过程与器官内部和器官之间的异常复杂因素相互作用,并且缺乏对衰老动力学的全面分析。

附:英文原文

Title: Ageing hallmarks exhibit organ-specific temporal signatures

Author: Nicholas Schaum, Benoit Lehallier, Oliver Hahn, Rbert Plovics, Shayan Hosseinzadeh, Song E. Lee, Rene Sit, Davis P. Lee, Patricia Morn Losada, Macy E. Zardeneta, Tobias Fehlmann, James T. Webber, Aaron McGeever, Kruti Calcuttawala, Hui Zhang, Daniela Berdnik, Vidhu Mathur, Weilun Tan, Alexander Zee, Michelle Tan, Angela Oliveira Pisco, Jim Karkanias, Norma F. Neff, Andreas Keller, Spyros Darmanis, Stephen R. Quake, Tony Wyss-Coray

Issue&Volume: 2020-07-15

Abstract: Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1—these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2—or ‘Mouse Ageing Cell Atlas’—which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions—including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue—including plasma cells that express immunoglobulin J—which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age.

DOI: 10.1038/s41586-020-2499-y

Source: https://www.nature.com/articles/s41586-020-2499-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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