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Series GSE218684 Query DataSets for GSE218684
Status Public on Jul 09, 2024
Title Ribosomal S6 kinase 1 regulates 'inflammaging' via the senescence secretome III.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Inhibition of the nutrient-responsive mTOR (mammalian target of rapamycin) signalling pathway including the key downstream S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice. However, the underlying mechanisms contributing to the profound age-related benefits observed with loss of S6K1 signalling are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory phenotype (termed the senescence-associated secretory phenotype, or SASP). Whileboth cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology the specific role of S6K1 signalling in these process have not been determined . Here, focussing on mouse liver a key target tissue for the beneficial health effects of loss of S6K1 signalling, we show that S6K1 deletion does not reduce senescence but ameliorates inflammation and immune cell infiltration in aged livers. Using human and mouse models of senescence, we demonstrated that reduced inflammation is a liver intrinsic effect associated with S6K deletion. Furthermore, gene expression analysis suggested that downregulated cGAS/STING and IRF3 activation might mediate the impaired SASP observed upon S6K deletion. Using a hepatic oncogene induced senescence model, we showed in vivo that S6K1 deletion results in reduced IRF3 activation, impaired production of cytokines such as IL1 and reduced immune infiltration. Overall, deletion of S6K reduces inflammation in the liver suggesting that suppression of the inflammatory SASP by S6K could contribute to explain the beneficial effects of inhibiting these pathways on healthspan and lifespan.
 
Overall design Transcriptomics data from whole liver homogenates from S6K1 WT and KO mice derived from young (90 days) and old (600 days) mice. Transcriptomics data from mouse embryonic fibroblasts undergoing replicative senescence or RAS-induced senescence derived from S6K1 WT/KO mice or S6K1/S6K2 WT/DKO mice.
 
Contributor(s) Withers DJ, Gil J, Heikenwalder M
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Submission date Nov 23, 2022
Last update date Jul 09, 2024
Contact name LMS Bioinformatics Core
E-mail(s) bioinformatics@lms.mrc.ac.uk
Organization name MRC London Institute of Medical Sciences
Department Bioinformatics Core
Street address Hammersmith Hospital Campus, Du Cane Road
City London
ZIP/Postal code W12 0NN
Country United Kingdom
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (22)
GSM6754799 MEFs - S6K1 WT Passage 3_SG02
GSM6754800 MEFs - S6K1 WT Passage 3_SG03
GSM6754801 MEFs - S6K1 WT Passage 3_SG04
Relations
BioProject PRJNA904791

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE218684_Rawcounts.csv.gz 976.3 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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