Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis.
Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis.
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DOI：
10.4049/jimmunol.2001022
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发表时间：
2021-02-15
期刊：
影响因子：
--
通讯作者：
Wilson CL
中科院分区：
文献类型：
--
作者：
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
适度的运动可以减少炎症，肝肿瘤和慢性肝病。关键分子变化包括脂质代谢、氧化损伤和衰老。增加NAD+，沉默调节蛋白活性，以及炎症和代谢重编程发生。乳腺癌相关的慢性炎症促进细胞衰老、慢性疾病、癌症和寿命缩短。在这项研究中，我们想探讨适度运动方案对炎症性肝病和肿瘤发生的影响。我们使用了一个自发性炎症、脂肪变性和癌症的模型（nfkb 1 −/−小鼠）来证明3个月的适度有氧运动是否足以抑制肝脏疾病和癌症的发展。在相对晚期的疾病阶段进行干预性运动，可有效减少组织炎症（肝、肺和胃）、氧化损伤和细胞衰老，逆转肝脂肪变性并预防肿瘤发展。这些益处的基础是驱动色氨酸转化为NAD+的酶的转录变化，这导致肝脏NAD+增加和NAD+依赖性脱乙酰酶沉默调节蛋白的活性升高。SIRT活性增加与炎症和代谢的关键转录调节因子NF-κB（p65）和PGC-1α的脱乙酰化增强相关。我们认为，适度的运动可以有效地重新编程预先建立的炎症和代谢病理老化与预防疾病的好处。
Moderate exercise reduces inflammaging, liver tumors, and chronic liver disease. Key molecular changes include lipid metabolism, oxidative damage, and senescence. Increased NAD+, sirtuin activity, and inflammatory and metabolic reprogramming occur. 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−/− 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.
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影响因子：
30.5
作者：
Finkin S;Yuan D;Stein I;Taniguchi K;Weber A;Unger K;Browning JL;Goossens N;Nakagawa S;Gunasekaran G;Schwartz ME;Kobayashi M;Kumada H;Berger M;Pappo O;Rajewsky K;Hoshida Y;Karin M;Heikenwalder M;Ben-Neriah Y;Pikarsky E
通讯作者：
Pikarsky E
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
影响因子：
16.6
作者：
Jurk, Diana;Wilson, Caroline;Passos, Joao F.;Oakley, Fiona;Correia-Melo, Clara;Greaves, Laura;Saretzki, Gabriele;Fox, Chris;Lawless, Conor;Anderson, Rhys;Hewitt, Graeme;Pender, Sylvia L. F.;Fullard, Nicola;Nelson, Glyn;Mann, Jelena;van de Sluis, Bart;Mann, Derek A.;von Zglinicki, Thomas
通讯作者：
von Zglinicki, Thomas
影响因子：
25.7
作者：
Elsharkawy, Ahmed M.;Oakley, Fiona;Lin, Feng;Packham, Graham;Mann, Derek A.;Mann, Jelena
通讯作者：
Mann, Jelena
影响因子：
3.3
作者：
de Araujo, Carla C.;Silva, Johnatas D.;Rocco, Patricia R. M.
通讯作者：
Rocco, Patricia R. M.