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Lookup NU author(s): Dr Arianna Bianchi, Dr Letizia Marchetti, Dr Hannah Paish, Dr Kile GreenORCiD, Dr Dina Tiniakos, Dr Joao Passos, Dr Diana JurkORCiD, Professor Derek Mann, Dr Caroline WilsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2021 The Authors.Age-related chronic inflammation promotes cellular senescence, chronic disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease and tumorigenesis. We used an established model of spontaneous inflammaging, steatosis, and cancer (nfkb12/2 mouse) to demonstrate whether 3 mo of moderate aerobic exercise was sufficient to suppress liver disease and cancer development. Interventional exercise when applied at a relatively late disease stage was effective at reducing tissue inflammation (liver, lung, and stomach), oxidative damage, and cellular senescence, and it reversed hepatic steatosis and prevented tumor development. Underlying these benefits were transcriptional changes in enzymes driving the conversion of tryptophan to NAD+, this leading to increased hepatic NAD+ and elevated activity of the NAD+-dependent deacetylase sirtuin. Increased SIRT activity was correlated with enhanced deacetylation of key transcriptional regulators of inflammation and metabolism, NF-kB (p65), and PGC-1a. We propose that moderate exercise can effectively reprogram pre-established inflammatory and metabolic pathologies in aging with the benefit of prevention of disease.
Author(s): Bianchi A, Marchetti L, Hall Z, Lemos H, Vacca M, Paish H, Green K, Elliott B, Tiniakos D, Passos JF, Jurk D, Mann DA, Wilson CL
Publication type: Article
Publication status: Published
Journal: Journal of Immunology
Year: 2021
Volume: 206
Issue: 4
Pages: 904-916
Online publication date: 01/02/2021
Acceptance date: 03/12/2020
Date deposited: 12/08/2021
ISSN (print): 0022-1767
ISSN (electronic): 1550-6606
Publisher: American Association of Immunologists
URL: https://doi.org/10.4049/jimmunol.2001022
DOI: 10.4049/jimmunol.2001022
PubMed id: 33441438
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