Ageing hallmarks exhibit organ-specific temporal signatures.
Ageing hallmarks exhibit organ-specific temporal signatures.
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DOI：
10.1038/s41586-020-2499-y
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发表时间：
2020-07
期刊：
影响因子：
64.8
通讯作者：
Wyss-Coray T
中科院分区：
文献类型：
--
作者：
Schaum N;Lehallier B;Hahn O;Pálovics R;Hosseinzadeh S;Lee SE;Sit R;Lee DP;Losada PM;Zardeneta ME;Fehlmann T;Webber JT;McGeever A;Calcuttawala K;Zhang H;Berdnik D;Mathur V;Tan W;Zee A;Tan M;Tabula Muris Consortium;Pisco AO;Karkanias J;Neff NF;Keller A;Darmanis S;Quake SR;Wyss-Coray T
衰老是世界范围内导致疾病和死亡的最大原因，了解相关过程可以极大地提高生活质量。虽然该领域已经确定了衰老损伤的主要类别，如细胞间通讯改变、蛋白质平衡丧失和线粒体功能受损，但这些有害过程在器官内部和器官之间的相互作用非常复杂。然而，对整个生物体衰老动态的全面分析一直缺乏。在这里，我们对小鼠一生中10个年龄的17个器官进行了大量rna测序和血浆蛋白质组学，并将这些发现与来自Tabula Muris Senis的数据结合起来。我们发现了以前未知的线性和非线性表达在衰老过程中的变化，这些变化聚集在惊人一致的轨迹组中，具有一致的生物学功能，包括细胞外基质调节、未折叠的蛋白质结合、线粒体功能以及炎症和免疫反应。值得注意的是，这些基因组在组织中表达相似，只是在发病年龄和幅度上有所不同。广泛的免疫细胞激活是特别明显的，并首先检测到白色脂肪库在中年。单细胞rna测序证实了脂肪T细胞和B细胞的积累，包括表达免疫球蛋白j的浆细胞，它们也同时在不同器官中积累。最后，我们展示了不同组织中的表达变化如何与血浆中相应的蛋白质水平高度相关，从而可能导致体循环老化。总之，这些数据表明了器官间和器官内衰老的相似但不同步的进展，从而为追踪老年健康下降的系统性来源提供了基础。
Aging is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function, these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide has been lacking. Here we performed bulk RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan, and integrated these findings with data from the companion Tabula Muris Senis. We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Widespread immune cell activation is especially pronounced and first detectable in white adipose depots during middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
3.9
作者：
Palmer, Allyson K.;Kirkland, James L.
通讯作者：
Kirkland, James L.
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
64.8
作者：
Tabula Muris Consortium
通讯作者：
Tabula Muris Consortium