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

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 (nfkb1 2/2 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.

Moderate endurance training reduced hepatic tumourigenesis associated with lower lactate overload compared to high‐intensity interval training

“…Consistent with our results, numerous studies have demonstrated that endurance training exhibits a protective effect against tumourigenesis 19,29,30 . Three months of moderate endurance exercise reduced inflammation and oxidative damage in Nfkb1 −/− mice, thereby reversing hepatic steatosis and preventing tumourigenesis 31 . Epidemiological investigation has also shown that middle‐distance runners and long‐distance runners have the lowest cancer incidence among athletes 32 .…”

Effect of Long-Term Exercise on Liver Lipid Metabolism in Chinese Patients With NAFLD: A Systematic Review and Meta-Analysis

“…Similar results to ours have been reported in other studies (Smart et al, 2018 ; Ye et al, 2019 ). This could be considered the ability of long-term exercise to improve the inflammatory state of the liver by increasing SIRT activity and enhancing the deacetylation of key transcription factors of inflammation and metabolism, such as NF-κB and PGC-1α (Bianchi et al, 2021 ), which in turn improves the state of the liver. Thus, the changes may have benefited from the improvement in inflammatory state of liver.…”

Telomere dysfunction in ageing and age-related diseases

“…Several pieces of evidence support a role for tDDR as a driver of ageing and age-associated diseases. First, interventions known to increase health span such as dietary restriction 41 , exercise 42 , rapamycin 43,44 and 17β-oestradiol 45 can reduce the frequency of cells with TAFs. Clearance of senescent cells with senolytic strategies reduces TAF numbers in vivo 36,37,41,46 .…”