Delayed development and lifespan extension as features of metabolic lifestyle alteration in C-elegans under dietary restriction
Delayed development and lifespan extension as features of metabolic lifestyle alteration in C-elegans under dietary restriction
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DOI：
10.1242/jeb.02492
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发表时间：
2006-10-15
影响因子：
2.8
通讯作者：
Conley, Catharine A.
中科院分区：
文献类型：
--
作者：
Szewczyk, Nathaniel J.;Udranszky, Ingrid A.;Conley, Catharine A.
对模式生物秀丽隐杆线虫的研究几乎完全利用细菌饮食的生长。这种培养对实验自动化提出了挑战，并将细菌代谢引入药物和环境毒理学研究中的次要问题。线虫的无菌培养可以避免这些问题，但过去的工作表明，线虫的无菌生长是不健康的。在这里，我们采用化学成分确定的液体培养基来培养秀丽隐杆线虫，发现与细菌饮食相比，其发育缓慢、繁殖力下降、寿命延长、脂质和蛋白质储存减少以及基因表达发生变化。这些变化似乎并不是与营养不良相关的随机病理，因为不存在与饥饿相关的发育迟缓，例如 L1 或 dauer 滞育。此外，无论饮食如何，发育和生殖期都是寿命的固定百分比，这表明这些改变是适应性的。我们认为线虫可以作为健康动物存在，具有至少两种不同的成年生活史。一种生活史使人口内在增长率最大化，另一种生活史使环境承载能力的利用效率最大化。微阵列分析揭示了 daf-16 和下游靶标的转录水平增加，过去的实验表明，作用于下游靶标的 DAF-16 (FOXO) 可以影响我们在维持培养基中看到的所有改变的表型。因此，饮食引起的生活史改变可能受到 DAF-16 的调节。我们的观察引入了一个强大的系统，用于对健康线虫进行自动化实验，并系统分析饮食对动物生理学的深远影响。
Studies of the model organism Caenorhabditis elegans have almost exclusively utilized growth on a bacterial diet. Such culturing presents a challenge to automation of experimentation and introduces bacterial metabolism as a secondary concern in drug and environmental toxicology studies. Axenic cultivation of C. elegans can avoid these problems, yet past work suggests that axenic growth is unhealthy for C. elegans. Here we employ a chemically defined liquid medium to culture C. elegans and find development slows, fecundity declines, lifespan increases, lipid and protein stores decrease, and gene expression changes relative to that on a bacterial diet. These changes do not appear to be random pathologies associated with malnutrition, as there are no developmental delays associated with starvation, such as L1 or dauer diapause. Additionally, development and reproductive period are fixed percentages of lifespan regardless of diet, suggesting that these alterations are adaptive. We propose that C. elegans can exist as a healthy animal with at least two distinct adult life histories. One life history maximizes the intrinsic rate of population increase, the other maximizes the efficiency of exploitation of the carrying capacity of the environment. Microarray analysis reveals increased transcript levels of daf-16 and downstream targets and past experiments demonstrate that DAF-16 (FOXO) acting on downstream targets can influence all of the phenotypes we see altered in maintenance medium. Thus, life history alteration in response to diet may be modulated by DAF-16. Our observations introduce a powerful system for automation of experimentation on healthy C. elegans and for systematic analysis of the profound impact of diet on animal physiology.