Bitto Alessandro, Wang Adrienne M, Bennett Christopher F, Kaeberlein Matt
Department of Pathology, University of Washington, Seattle, Washington 98195.
Cold Spring Harb Perspect Med. 2015 Nov 2;5(11):a025114. doi: 10.1101/cshperspect.a025114.
The mechanisms underlying biological aging have been extensively studied in the past 20 years with the avail of mainly four model organisms: the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster, and the domestic mouse Mus musculus. Extensive research in these four model organisms has identified a few conserved genetic pathways that affect longevity as well as metabolism and development. Here, we review how the mechanistic target of rapamycin (mTOR), sirtuins, adenosine monophosphate-activated protein kinase (AMPK), growth hormone/insulin-like growth factor 1 (IGF-1), and mitochondrial stress-signaling pathways influence aging and life span in the aforementioned models and their possible implications for delaying aging in humans. We also draw some connections between these biochemical pathways and comment on what new developments aging research will likely bring in the near future.
在过去20年里,借助主要四种模式生物,对生物衰老的潜在机制进行了广泛研究:芽殖酵母酿酒酵母、线虫秀丽隐杆线虫、果蝇黑腹果蝇和家鼠小家鼠。对这四种模式生物的广泛研究已经确定了一些影响寿命以及新陈代谢和发育的保守遗传途径。在这里,我们综述雷帕霉素机制性靶点(mTOR)、沉默调节蛋白、腺苷单磷酸激活蛋白激酶(AMPK)、生长激素/胰岛素样生长因子1(IGF-1)和线粒体应激信号通路如何影响上述模型中的衰老和寿命,以及它们对延缓人类衰老的可能影响。我们还梳理了这些生化途径之间的一些联系,并对衰老研究在不久的将来可能带来的新进展进行评论。