Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
J Gerontol A Biol Sci Med Sci. 2022 Jun 1;77(6):1112-1120. doi: 10.1093/gerona/glac040.
Like other biological processes, aging is not random but subject to molecular control. Natural products that modify core metabolic parameters, including fat content, may provide entry points to extend animal life span and promote healthy aging. Here, we show that a botanical extract from Artemisia scoparia (SCO), which promotes fat storage and metabolic resiliency in mice, extends the life span of the nematode Caenorhabditis elegans by up to 40%. Notably, this life-span extension depends significantly on SCO's effects on fat; SCO-treated worms exhibit heightened levels of unsaturated fat, and inhibition of Δ9 desaturases, which oversee biosynthesis of monounsaturated fatty acids, prevents SCO-dependent fat accumulation and life-span extension. At an upstream signaling level, SCO prompts changes to C. elegans fat regulation by stimulating nuclear translocation of transcription factor DAF-16/FOXO, an event that requires AMP-activated protein kinase under this condition. Importantly, animals treated with SCO are not only long-lived but also show improved stress resistance in late adulthood, suggesting that this fat-promoting intervention may enhance some aspects of physiological health in older age. These findings identify SCO as a natural product that can modify fat regulation for longevity benefit and add to growing evidence indicating that elevated fat can be prolongevity in some circumstances.
与其他生物过程一样,衰老不是随机的,而是受分子控制的。能够改变核心代谢参数(包括脂肪含量)的天然产物可能为延长动物寿命和促进健康衰老提供切入点。在这里,我们表明,来自青蒿(Artemisia scoparia)的植物提取物(SCO)可促进小鼠脂肪储存和代谢弹性,可将秀丽隐杆线虫的寿命延长多达 40%。值得注意的是,这种寿命延长在很大程度上取决于 SCO 对脂肪的影响;SCO 处理的线虫表现出更高水平的不饱和脂肪,而抑制 Δ9 去饱和酶(负责单不饱和脂肪酸生物合成)可防止 SCO 依赖性脂肪积累和寿命延长。在信号转导的上游水平,SCO 通过刺激转录因子 DAF-16/FOXO 的核易位来促使线虫脂肪调节发生变化,这种事件在这种情况下需要 AMP 激活的蛋白激酶。重要的是,用 SCO 处理的动物不仅寿命长,而且在老年后期还表现出更好的应激抗性,这表明这种促进脂肪的干预措施可能会增强老年时某些生理健康方面。这些发现确定了 SCO 是一种可以改变脂肪调节以延长寿命的天然产物,并为越来越多的证据增加了内容,这些证据表明在某些情况下,提高脂肪含量可以延长寿命。