AMPK通过抑制NLRP3炎症小体参与延缓衰老过程

衰老是在细胞、组织和器官水平上发生的生理性内稳态的渐进性损害过程。就代谢角度而言,该过程主要表现为体成分、胰岛素抵抗、自噬功能障碍、线粒体和炎症反应的变化,其中涉及生长激素、胰岛素/胰岛素样生长因子1及各种能量感应系统如AMP活化蛋白激酶(AMP-activated protein kinase,AMPK).

Delaying aging of AMPK by inhibiting NLRP3 inflammasome

AMP-activated protein kinase(AMPK)is a central regulator of many metabolic pathways involved in the pathophysiological processes of aging and related diseases,and has become an important integrator influencing inflammation(including inflammasome). The nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome has recently become a highly concerned marker of stress and metabolic risk. It is associated with neurodegenerative and cardiovascular diseases and type 2 diabetes mellitus. However,the signal pathways regulating NLRP3 inflammasome have not yet been clarified. Studies have shown that many AMPK-dependent signaling pathways,such as autophagy(including mitophagy)and endoplasmic reticulum stress(ERS),regulate the expression of NLRP3 inflammasome during aging. Inhibiting the expression of NLRP3 seems to be a common factor in many complex-mediated aging responses. Therefore,eliminating the common triggers of autophagy/ERS and NLRP3 inflammasome,and suppressing the signal cascade of inflammatory cytokines such as IL-1β and TNF-α,will be an important research direction to explore new anti-aging strategies.