Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Exp Gerontol. 2011 Jun;46(6):441-52. doi: 10.1016/j.exger.2011.01.005. Epub 2011 Feb 2.
Medicinal benefits of Allium vegetables, such as garlic, have been noted throughout recorded history, including protection against cancer and cardiovascular disease. We now demonstrate that garlic constituent diallyl trisulfide (DATS) increases longevity of Caenorhabditis elegans by affecting the skn-1 pathway. Treatment of worms with 5-10 μM DATS increased worm mean lifespan even when treatment is started during young adulthood. To explore the mechanisms involved in the DATS-mediated increase in longevity, we treated daf-2, daf-16, and eat-2 mutants and found that DATS increased the lifespan of daf-2 and daf-16 mutants, but not the eat-2 mutants. Microarray experiments demonstrated that a number of genes regulated by oxidative stress and the skn-1 transcription factor were also changed by DATS treatment. Consistently, DATS treatment leads to the induction of the skn-1 target gene gst-4, and this induction was dependent on skn-1. We also found that the effects of DATS on worm lifespan depend on skn-1 activity in both in the intestine and ASI neurons. Together our data suggest that DATS is able to increase worm lifespan by enhancing the function of the pro-longevity transcription factor skn-1.
大蒜等葱属蔬菜的药用功效在有记载的历史中一直受到关注,包括预防癌症和心血管疾病。我们现在证明,大蒜成分二烯丙基三硫化物(DATS)通过影响 skn-1 途径来延长秀丽隐杆线虫的寿命。即使在成年早期开始治疗,用 5-10 μM DATS 处理蠕虫也会增加蠕虫的平均寿命。为了探索 DATS 介导的寿命延长所涉及的机制,我们处理了 daf-2、daf-16 和 eat-2 突变体,并发现 DATS 增加了 daf-2 和 daf-16 突变体的寿命,但对 eat-2 突变体没有影响。微阵列实验表明,许多受氧化应激和 skn-1 转录因子调节的基因也因 DATS 处理而发生变化。一致地,DATS 处理导致 skn-1 靶基因 gst-4 的诱导,并且这种诱导依赖于 skn-1。我们还发现,DATS 对蠕虫寿命的影响取决于肠道和 ASI 神经元中 skn-1 的活性。我们的数据表明,DATS 能够通过增强长寿转录因子 skn-1 的功能来延长蠕虫的寿命。