蛋白质与植物基因研究国家重点实验室顾军课题组研究衰老与炎症机制的研究论文于2011年2月20日在《自然—细胞生物学》Nature Cell Biology 在线发表。
顾军课题组的研究工作首次揭示了衰老的炎症机制及抗衰老蛋白是如何通过抑制炎症反应来拮抗衰老的。虽然人们很早就认识到炎症是细胞衰老及机体老化的伴随反应，并起着维持和促进衰老及老化的作用。然而，对衰老的炎症机制一直很不清楚。
顾军实验室的研究发现RIG-I/MAVS信号通路介导了衰老及老化的炎症反应。在MAVS缺失的细胞和小鼠中，衰老和老化伴随的炎症反应明显下降。在复制性衰老的细胞中干涉RIG-I，可以降低衰老的炎性反应并延缓细胞衰老的进程。
进一步的研究发现抗衰老蛋白klotho是RIG-I的抑制因子，可以拮抗RIG-I诱导的衰老性炎症反应。在klotho敲除的小鼠中，炎症反应显著增强。在复制性衰老细胞中表达外源的klotho，可以拮抗细胞衰老的进程。同时他们的研究还发现随着衰老的进程，RIG-I表达水平逐渐升高，而抗衰老蛋白klotho的水平逐渐降低。
这一发现提示衰老是一个炎症失衡的自然程序。随着衰老的发生，细胞和机体逐渐向致炎过程倾斜，抑炎作用逐渐减弱，最终导致衰老的慢性炎症。这就很好的解释了为什么衰老是炎症相伴的自然现象。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
