2009年2月25日星期三

Nature:蛔虫的启示 少食而长寿


为了在严酷环境中生存,蛔虫的幼虫能进入一种所谓的“多尔(dauer)”状态,在处于这种状态期间,它们不吃东西,但仍能活动,对压力具有抵抗力,而且极为长寿。
在一个典型的“多尔”幼虫体内,胰岛素类信号作用减少,营养储备充分,而且其代谢过程发生全面变化。Patrick Narbonne 和 Richard Roy发现,如果没有AMPK (LKB1)信号作用,“多尔”幼虫会迅速耗尽其所储存的能量,并且会由于重要器官衰竭而过早死亡。在一个正常的“多尔”幼虫中,LKB1/AMPK通过减慢甘油三酸酯的水解来保证幼虫不需要食物而能长寿和具有活力,从而使体内所存储的脂肪能够维持更长时间,同时保持正确的渗透调节(osmoregulation)。这项工作触及在关于 衰老 、 糖尿病 和肥胖症研究中所涉及的体系。( 生物谷 Bioon.com)
生物谷 推荐原始出处:
Nature 457, 210-214 (8 January 2009) doi:10.1038/nature07536
Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival
Patrick Narbonne1 & Richard Roy1
1 Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada
Many organisms can enter a dormant state or diapause to survive harsh environmental conditions for extended durations. When Caenorhabditis elegans larvae enter dauer they arrest feeding but remain active and motile, yet become stress-resistant, extremely long-lived and non-ageing1. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism2, 3, 4, 5, yet the precise molecular and physiological processes that enable long-term survival in the absence of caloric intake remain largely unknown. We show here that C. elegans larvae that lack LKB1/AMPK (AMP-activated protein kinase) signalling enter dauer normally, but then rapidly consume their stored energy and prematurely expire following vital organ failure. We found that this signalling pathway acts in adipose-like tissues to downregulate triglyceride hydrolysis so that these lipid reserves are rationed to last the entire duration of the arrest. Indeed, the downregulation of adipose triglyceride lipase (ATGL-1) activity suppresses both the rapid depletion of stored lipids and reduced life span of AMPK mutant dauers, while AMPK directly phosphorylates ATGL-1. Finally, we show that the slow release of energy during dauer is critical for appropriate long-term osmoregulation, which fails as triglyceride resources become depleted. These mechanisms may be essential for survival through diapause, hibernation, or long-term fasting in diverse organisms and may also underlie AMPK-dependent life span extension.

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