蛋白質(zhì)與植物基因研究國家重點(diǎn)實(shí)驗(yàn)室顧軍課題組研究衰老與炎癥機(jī)制的研究論文于2011年2月20日在《自然—細(xì)胞生物學(xué)》Nature Cell Biology 在線發(fā)表,。
顧軍課題組的研究工作首次揭示了衰老的炎癥機(jī)制及抗衰老蛋白是如何通過抑制炎癥反應(yīng)來拮抗衰老的。雖然人們很早就認(rèn)識到炎癥是細(xì)胞衰老及機(jī)體老化的伴隨反應(yīng),，并起著維持和促進(jìn)衰老及老化的作用,。然而，對衰老的炎癥機(jī)制一直很不清楚,。
顧軍實(shí)驗(yàn)室的研究發(fā)現(xiàn)RIG-I/MAVS信號通路介導(dǎo)了衰老及老化的炎癥反應(yīng),。在MAVS缺失的細(xì)胞和小鼠中，衰老和老化伴隨的炎癥反應(yīng)明顯下降,。在復(fù)制性衰老的細(xì)胞中干涉RIG-I,，可以降低衰老的炎性反應(yīng)并延緩細(xì)胞衰老的進(jìn)程。
進(jìn)一步的研究發(fā)現(xiàn)抗衰老蛋白klotho是RIG-I的抑制因子,，可以拮抗RIG-I誘導(dǎo)的衰老性炎癥反應(yīng)。在klotho敲除的小鼠中,，炎癥反應(yīng)顯著增強(qiáng),。在復(fù)制性衰老細(xì)胞中表達(dá)外源的klotho，可以拮抗細(xì)胞衰老的進(jìn)程,。同時(shí)他們的研究還發(fā)現(xiàn)隨著衰老的進(jìn)程,，RIG-I表達(dá)水平逐漸升高，而抗衰老蛋白klotho的水平逐漸降低,。
這一發(fā)現(xiàn)提示衰老是一個(gè)炎癥失衡的自然程序,。隨著衰老的發(fā)生，細(xì)胞和機(jī)體逐漸向致炎過程傾斜,，抑炎作用逐漸減弱,，最終導(dǎo)致衰老的慢性炎癥。這就很好的解釋了為什么衰老是炎癥相伴的自然現(xiàn)象,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature Cell Biology doi:10.1038/ncb2167
Klotho suppresses RIG-I-mediated senescence-associated inflammation
Feng Liu,1, 2 Su Wu,1, 2 Hongwei Ren1 & Jun Gu1, 3
It is well known that aged or senescent cells develop a complex senescence-associated secretory phenotype (SASP), which is observed both in culture and in vivo. However, the mechanisms underlying the induction of the SASP are largely unknown. We demonstrate that retinoic-acid-inducible gene-I (RIG-I) is induced through the ataxia telangiectasia mutated–interferon regulatory factor 1 (ATM–IRF1) axis in senescent cells and that RIG-I signalling mediates the expression of two important mediators of inflammation, interleukin-6 (IL-6) and IL-8. Klotho has been associated with ageing. We show here that the intracellular, but not the secreted, form of klotho interacts with RIG-I and that this interaction inhibits RIG-I-induced expression of IL-6 and IL-8 both in vitro and in vivo. Our study uncovers a mechanism in which klotho functions as an anti-ageing factor through the suppression of RIG-I-mediated inflammation.
