Ageing hallmarks exhibit organ-specific temporal signatures.

Nature
Nicholas SchaumTony Wyss-Coray

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 cell...Continue Reading

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Citations

Jul 29, 2020·Rejuvenation Research·James W Larrick, Andrew R Mendelsohn
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Datasets Mentioned

BETA
GSE132040

Methods Mentioned

BETA
scRNA-seq
protein folding
dissection
Smart-seq2
RNA-seq
FACS
PCA

Software Mentioned

topGO
Kohonen R package
Deseq2
Rstudio scripts
GAT
clusterprofiler
SomaLogic
R package destiny
R TopGO package
SCTransform

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