Chronic inflammation induces telomere dysfunction and accelerates ageing in mice.
Chronic inflammation induces telomere dysfunction and accelerates ageing in mice.
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DOI：
10.1038/ncomms5172
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发表时间：
2014-06-24
影响因子：
16.6
通讯作者：
von Zglinicki, Thomas
中科院分区：
文献类型：
--
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
慢性炎症与正常和病理性衰老有关。在这里，我们展示了由转录因子NF-κB的nfkb1亚单位敲除引起的慢性、进行性低度炎症导致小鼠过早衰老。我们还表明，这些小鼠的肝脏和肠道再生减少。NFKB1DNA成纤维细胞通过NF-−/−B、COX-2和ROS的自分泌和旁分泌反馈，使细胞衰老加剧，从而稳定κ损伤。小鼠的抗炎或抗氧化治疗可以阻止端粒功能障碍的衰老细胞在nfkb1−/−组织中的优先积累，这挽救了组织再生的潜力。肝脏和肠腺中衰老细胞的频率可以定量预测短寿命和长寿命小鼠的平均寿命和最长寿命。这些数据表明，在没有任何其他遗传或环境因素的情况下，全身性慢性炎症可以通过ROS介导的加剧端粒功能障碍和细胞衰老来加速衰老。许多与年龄相关的疾病都与慢性炎症有关。这里，Jurk等人。使用慢性、低级别炎症的小鼠模型来支持这样的模型，通过该模型，这种炎症促进氧化应激、端粒功能障碍和细胞衰老的恶性循环，从而加速衰老过程。
Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing in mice. We also show that these mice have reduced regeneration in liver and gut. nfkb1−/− fibroblasts exhibit aggravated cell senescence because of an enhanced autocrine and paracrine feedback through NF-κB, COX-2 and ROS, which stabilizes DNA damage. Preferential accumulation of telomere-dysfunctional senescent cells in nfkb1−/− tissues is blocked by anti-inflammatory or antioxidant treatment of mice, and this rescues tissue regenerative potential. Frequencies of senescent cells in liver and intestinal crypts quantitatively predict mean and maximum lifespan in both short- and long-lived mice cohorts. These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor. Many age-related diseases are associated with chronic inflammation. Here Jurk et al. use a mouse model of chronic, low-grade inflammation to support a model by which such inflammation promotes a vicious cycle of oxidative stress, telomere dysfunction and cell senescence that accelerates the ageing process.
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影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
DOI：
10.1093/geronj/45.4.b129
发表时间：
1990-07-01
期刊：
JOURNALS OF GERONTOLOGY
影响因子：
--
作者：
CHEN, TS;CURRIER, GJ;WABNER, CL
通讯作者：
WABNER, CL
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：
56.9
作者：
Herbig, U;Ferreira, M;Sedivy, JM
通讯作者：
Sedivy, JM