Aging networks in Caenorhabditis elegans:: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways
Aging networks in Caenorhabditis elegans:: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways
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DOI：
10.1111/j.1474-9726.2006.00205.x
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发表时间：
2006-04-01
期刊：
影响因子：
7.8
通讯作者：
DiStefano, PS
中科院分区：
文献类型：
--
作者：
Curtis, R;O'Connor, G;DiStefano, PS
低等生物的分子遗传学已经阐明了调节衰老过程的途径。在某些情况下，进化上保守的基因和途径也被证明可以调节哺乳动物的寿命。许多已知影响寿命的基因产物都与能量代谢的控制密切相关，包括燃料传感器amp活化蛋白激酶（AMPK）。我们之前已经证明，在秀丽隐杆线虫中，过表达AMPK亚基，即aak-2，可以延长寿命。在这里，我们展示了aak-2与其他已知控制蠕虫衰老的途径的相互作用。daf-2/胰岛素样信号突变引起的寿命延长高度依赖于aak-2，脱乙酰酶sir-2.1过表达引起的寿命延长也是如此。同样，线粒体突变（isp-1和clk-1）延长寿命也部分需要aak-2。相反，缺乏种系干细胞的突变体（glp-1）或进食反应突变体（eat-2）不需要aak-2来延长寿命。这些结果表明，衰老是由重叠但不同的途径控制的，AMPK/aak-2代表了控制衰老的进化保守生化途径网络中的一个节点。
Molecular genetics in lower organisms has allowed the elucidation of pathways that modulate the aging process. In certain instances, evolutionarily conserved genes and pathways have been shown to regulate lifespan in mammals as well. Many gene products known to affect lifespan are intimately involved in the control of energy metabolism, including the fuel sensor AMP-activated protein kinase (AMPK). We have shown previously that over-expression of an AMPK a subunit in Caenorhabditis elegans, designated aak-2, increases lifespan. Here we show the interaction of aak-2 with other pathways known to control aging in worms. Lifespan extension caused by daf-2/insulin-like signaling mutations was highly dependent on aak-2, as was the lifespan extension caused by overexpression of the deacetylase, sir-2.1. Similarly, there was partial requirement for aak-2 in lifespan extension by mitochondrial mutations (isp-1 and clk-1). Conversely, aak-2 was not required for lifespan extension in mutants lacking germline stem cells (glp-1) or mutants of the eating response (eat-2). These results show that aging is controlled by overlapping but distinct pathways and that AMPK/aak-2 represents a node in a network of evolutionarily conserved biochemical pathways that control aging.