Lee Garrick D, Wilson Mark A, Zhu Min, Wolkow Catherine A, de Cabo Rafael, Ingram Donald K, Zou Sige
Laboratory of Experimental Gerontology, National Institute on Aging, Balimore, MD 21224, USA.
Aging Cell. 2006 Dec;5(6):515-24. doi: 10.1111/j.1474-9726.2006.00241.x. Epub 2006 Nov 10.
Dietary restriction (DR) is well known as a nongenetic intervention that robustly extends lifespan in a variety of species; however, its underlying mechanisms remain unclear. We have found in Caenorhabditis elegans that dietary deprivation (DD) during adulthood, defined as removal of their food source Escherichia coli after the completion of larval development, increased lifespan and enhanced thermotolerance and resistance to oxidative stress. DD-induced longevity was independent of one C. elegans SIRTUIN, sir-2.1, which is required for the effects of DR, and was independent of the daf-2/insulin-like signaling pathway that independently regulates longevity and larval diapause in C. elegans. DD did not significantly alter lifespan of fem-1(hc17); eat-2(ad465) worms, a genetic model of DR. These findings suggest that DD and DR share some downstream effectors. In addition, DD was detrimental for longevity when imposed on reproductively active young adults, suggesting that DD may only be beneficial in the absence of competing metabolic demands, such as fertility. Adult-onset DD offers a new paradigm for investigating dietary regulation of longevity in C. elegans. This study presents the first evidence that long-term DD, instead of being detrimental, can extend lifespan of a multicellular adult organism.
饮食限制(DR)作为一种非基因干预手段,在多种物种中都能显著延长寿命,这一点广为人知;然而,其潜在机制仍不清楚。我们在秀丽隐杆线虫中发现,成年期的食物剥夺(DD),即幼虫发育完成后去除其食物来源大肠杆菌,可延长寿命,并增强耐热性和抗氧化应激能力。DD诱导的长寿独立于一种秀丽隐杆线虫的沉默信息调节因子sir-2.1,而sir-2.1是DR发挥作用所必需的,并且独立于秀丽隐杆线虫中独立调节寿命和幼虫滞育的daf-2/胰岛素样信号通路。DD并未显著改变fem-1(hc17); eat-2(ad465)蠕虫(一种DR的遗传模型)的寿命。这些发现表明DD和DR共享一些下游效应因子。此外,当对生殖活跃的年轻成虫施加DD时,对长寿是有害的,这表明DD可能仅在没有诸如生育力等竞争性代谢需求的情况下才有益。成年期开始的DD为研究秀丽隐杆线虫中寿命的饮食调节提供了一种新范式。这项研究首次证明,长期的DD并非有害,反而可以延长多细胞成年生物的寿命。