Please use this identifier to cite or link to this item: doi:10.22028/D291-35956
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Title: Ageing hallmarks exhibit organ-specific temporal signatures
Author(s): Schaum, Nicholas
Lehallier, Benoit
Hahn, Oliver
Pálovics, Róbert
Hosseinzadeh, Shayan
Lee, Song E.
Sit, Rene
Lee, Davis P
Losada, Patricia Morán
Zardeneta, Macy E.
Fehlmann, Tobias
Webber, James T.
McGeever, Aaron
Calcuttawala, Kruti
Zhang, Hui
Berdnik, Daniela
Mathur, Vidhu
Tan, Weilun
Zee, Alexander
Tan, Michelle
Pisco, Angela Oliveira
Karkanias, Jim
Neff, Norma F.
Keller, Andreas
Darmanis, Spyros
Quake, Stephen R.
Wyss-Coray, Tony
Language: English
Title: Nature
Volume: 583
Issue: 7817
Pages: 596–602
Publisher/Platform: Springer Nature
Year of Publication: 2020
Publikation type: Journal Article
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 identifed—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 fndings 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 infammatory and immune response. Notably, these gene sets show similar expression across tissues, difering only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is frst detectable in white adipose depots during middle age. Single-cell RNA sequencing confrms 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 of the first publication: 10.1038/s41586-020-2499-y
URL of the first publication: https://www.nature.com/articles/s41586-020-2499-y
Link to this record: hdl:20.500.11880/32772
http://dx.doi.org/10.22028/D291-35956
ISSN: 1476-4687
0028-0836
Date of registration: 11-Apr-2022
Faculty: M - Medizinische Fakultät
Department: M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
Professorship: M - Univ.-Prof. Dr. Andreas Keller
Collections:Die Universitätsbibliographie

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