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

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, stea...

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Veröffentlicht in:The Journal of immunology (1950) 2021-02, Vol.206 (4), p.904-916
Hauptverfasser: Bianchi, Arianna, Marchetti, Letizia, Hall, Zoe, Lemos, Henrique, Vacca, Michele, Paish, Hannah, Green, Kile, Elliott, Bronte, Tiniakos, Dina, Passos, João F, Jurk, Diana, Mann, Derek A, Wilson, Caroline L
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container_issue 4
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container_title The Journal of immunology (1950)
container_volume 206
creator Bianchi, Arianna
Marchetti, Letizia
Hall, Zoe
Lemos, Henrique
Vacca, Michele
Paish, Hannah
Green, Kile
Elliott, Bronte
Tiniakos, Dina
Passos, João F
Jurk, Diana
Mann, Derek A
Wilson, Caroline L
description 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 ( 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-κB (p65), and PGC-1α. We propose that moderate exercise can effectively reprogram pre-established inflammatory and metabolic pathologies in aging with the benefit of prevention of disease.
doi_str_mv 10.4049/jimmunol.2001022
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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 ( 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-κB (p65), and PGC-1α. 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subjects Aging - genetics
Aging - immunology
Aging - pathology
Animals
Carcinogenesis - immunology
Carcinogenesis - pathology
Cellular Senescence - immunology
Fatty Liver - immunology
Fatty Liver - pathology
Fatty Liver - prevention & control
Inflammation - genetics
Inflammation - immunology
Inflammation - pathology
Liver Neoplasms - genetics
Liver Neoplasms - immunology
Liver Neoplasms - pathology
Liver Neoplasms - prevention & control
Mice
Mice, Knockout
NF-kappa B p50 Subunit - genetics
NF-kappa B p50 Subunit - immunology
Physical Conditioning, Animal
Tumor Immunology
title Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis
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