能量代谢重编程促进衰老-肿瘤发生的病机探讨  

Pathogenesis Discussion of Energy Metabolism Reprogramming Promoting Aging-Tumorigenesis

作　　者：靖林林[1] 姚学清[2] 王俊江[2] 孙学刚[1] JING Lin-lin;YAO Xue-qing;WANG Jun-jiang;SUN Xue-gang(Traditional Chinese Medicine Integrated Hospital,Southern Medical University,Guangzhou 510515,Guangzhou,China;Department of Gastrointestinal Surgery,Guangdong General Hospital,Guangzhou 510120,China)

机构地区：[1]南方医科大学,广州510515 [2]广东省人民医院胃肠外科,广州510080

出　　处：《中国中医基础医学杂志》2018年第8期1095-1097,共3页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金面上项目(81573848;81774172);广东省自然科学基金项目(2014A030313323);广东省中医药局科研项目(20161161;20162002);广州市科技计划(201607010146);南方医科大学科研启动计划(CX2015N008);科技开发培育计划(C1033034)

摘　　要：衰老促进肿瘤发生,衰老进程中线粒体损伤及其能量代谢障碍导致正气亏虚,脾肾亏虚则是因虚致癌的脏腑病机。线粒体与细胞核之间的信号传递和基因之间的协同表达是线粒体能量代谢调节的中心,体现脾肾相互滋生、共同扶助正气。辅活化因子如PGC-1α在衰老时功能失调,核-线粒体通讯功能障碍可能是脾肾亏虚能量代谢障碍的重要机制。衰老进程中NAD+水平日益降低,导致Sirtuins家族成员功能减退,上调HIF-1α,通过表观遗传修饰诱导假性缺氧、核-线粒体通讯障碍,产生以糖酵解为主的能量代谢重编程,即使不足以产生肿瘤,却是诱导肿瘤生长所必须。因此健脾补肾通过调节衰老进程中的表观遗传修饰,有可能延缓或者逆转"衰老-肿瘤发生"进程。Aging drives tumorigenesis. Mitochondria damage and subsequent energy metabolism dysfunction induce deficiency of healthy-Qi. Deficiency of spleen and kidney is the main visceral pathogenesis of geroncogenesis. Signal transduction and coordination of gene expression between mitochondrial and nuclear genomes are pivotal for regulation of mitochondrial energy metabolism. It characterizes the mutual breeding between spleen and kidney to support healthy-Qi.The dysfunction of coactivators,such as peroxisome proliferator-activated receptor γ coactivator-1 α（ PGC-1α） suppresses the communication between neclear and mitochondria. Subsequently,the energy metabolism would be impaired to cause deficiency of spleen and kidney. The decline of nicotinamide adenine dinucleotide（ NAD＋） inhibits the function of Sirtuins and elevates hypoxia-inducible factor 1α（ HIF-1α）. It induces pseudohypoxia and metabolic reprogramming towards aerobic glycolysis which is necessary,even not enough,for the tumorigenesis. Tonifying spleen and nourishing kidney might be a candidate method to delay or reverse geroncogenesis through regulation of epigenetic modification during aging.

关 键 词：脾肾亏虚 细胞核-线粒体通讯 表观遗传学 衰老-肿瘤发生 能量代谢 

分 类 号：R222.19[医药卫生—中医基础理论]