Moderate exercise inhibits age-related inflammation, liver steatosis, senescence, and tumorigenesis

Arianna Bianchi, Letizia Marchetti, Zoe Hall, Henrique Lemos, Michele Vacca, Hannah Paish, Kile Green, Bronte Elliott, Dina Tiniakos, João F. Passos, Diana Jurk, Derek A. Mann, Caroline L. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)904-916
Number of pages13
JournalJournal of Immunology
Volume206
Issue number4
DOIs
StatePublished - Feb 15 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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