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Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction

Rasa, Seyed Mohammad Mahdi, Annunziata, Francesco, Krepelova, Anna, Nunna, Suneetha, Omrani, Omid, Gebert, Nadja, Adam, Lisa, Käppel, Sandra, Hoehn, Sven, Donati, Giacomo, Jurkowski, Tomasz Piotr ORCID: https://orcid.org/0000-0002-2012-0240, Rudolph, Karl Lenhard, Ori, Alessandro and Neri, Francesco 2022. Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction. Cell Reports 39 (13) , 111017. 10.1016/j.celrep.2022.111017

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Abstract

Aging is characterized by a chronic low-grade inflammation known as inflammaging in multiple tissues, representing a risk factor for age-related diseases. Dietary restriction (DR) is the best-known non-invasive method to ameliorate aging in many organisms. However, the molecular mechanism and the signaling pathways that drive inflammaging across different tissues and how they are modulated by DR are not yet understood. Here we identify a multi-tissue gene network regulating inflammaging. This network is characterized by chromatin opening and upregulation in the transcription of innate immune system receptors and by activation of interferon signaling through interferon regulatory factors, inflammatory cytokines, and Stat1-mediated transcription. DR ameliorates aging-induced alterations of chromatin accessibility and RNA transcription of the inflammaging gene network while failing to rescue those alterations on the rest of the genome. Our results present a comprehensive understanding of the molecular network regulating inflammation in aging and DR and provide anti-inflammaging therapeutic targets.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: User License Creative Commons Attribution (CC BY 4.0)
Publisher: Cell Press
ISSN: 2211-1247
Date of First Compliant Deposit: 13 July 2022
Date of Acceptance: 7 June 2022
Last Modified: 10 Nov 2022 11:37
URI: https://orca.cardiff.ac.uk/id/eprint/151265

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