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Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis

Lookup NU author(s): Dr Arianna Bianchi, 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.

Publication metadata

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


DOI: 10.4049/jimmunol.2001022

PubMed id: 33441438


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Funder referenceFunder name
C18342/A23390Cancer Research UK CRUK (open competition)
MR/R023026/1Medical Research Council (MRC)