Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans.
Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans.
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DOI：
10.1186/1471-2180-12-49
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发表时间：
2012-03-27
期刊：
影响因子：
4.2
通讯作者：
Blaser MJ
中科院分区：
文献类型：
--
作者：
Portal-Celhay C;Bradley ER;Blaser MJ
理解诸如衰老等复杂过程的一个强有力的方法是使用易于遗传操纵的模式生物，并寻找相关的表型来测量。秀丽隐杆线虫特别适合于衰老的研究，因为已经确定了许多影响其寿命的单基因突变;它拥有一个先天免疫系统，采用进化上保守的影响寿命的信号通路。随着蠕虫年龄的增长，细菌在肠道中积累。然而，蠕虫基因型，寿命和肠腔细菌负荷之间的定量关系尚未研究。我们假设，肠道免疫力在老年动物中效率较低，导致细菌积累增加，寿命缩短。为了解决这个问题，我们评估了蠕虫控制细菌积累的能力，作为肠道免疫的功能标志。我们发现，随着成虫年龄的增长，几个C。elegans基因型显示控制肠道细菌积累的能力降低。我们提供的证据表明，肠道细菌负荷，调节肠道免疫，是一个重要的致病因素的寿命决定;细菌菌株，蠕虫基因型，和生物年龄，所有的一致行动的影响。总的来说，这些研究将注意力集中在蠕虫肠道上，因为在积累细菌种群的情况下，肠道是影响寿命的一个位点。进一步研究确定细菌种类和宿主免疫之间的相互作用，在C。秀丽线虫可能提供对衰老和与年龄有关的疾病的一般机制的见解。
A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.
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影响因子：
56.9
作者：
Garsin, DA;Villanueva, JM;Ausubel, FM
通讯作者：
Ausubel, FM
影响因子：
9.8
作者：
Félix MA;Ashe A;Piffaretti J;Wu G;Nuez I;Bélicard T;Jiang Y;Zhao G;Franz CJ;Goldstein LD;Sanroman M;Miska EA;Wang D
通讯作者：
Wang D
DOI：
10.1895/wormbook.1.137.1
发表时间：
2008-01-24
期刊：
WormBook : the online review of C. elegans biology
影响因子：
--
作者：
Collins, James J;Huang, Cheng;Kornfeld, Kerry
通讯作者：
Kornfeld, Kerry
影响因子：
56.9
作者：
Ewbank, JJ;Barnes, TM;Hekimi, S
通讯作者：
Hekimi, S
影响因子：
3.1
作者：
Crews, Douglas E.
通讯作者：
Crews, Douglas E.