A High-Throughput Screen for Chemicals that Increase the Lifespan of Caenorhabditis elegans
A High-Throughput Screen for Chemicals that Increase the Lifespan of Caenorhabditis elegans
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DOI：
10.1111/j.1749-6632.2009.04377.x
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Buck, Linda B.
中科院分区：
文献类型：
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作者：
Petrascheck, Michael;Ye, Xiaolan;Buck, Linda B.
衰老研究的一个长期目标是找到可以延缓衰老和年龄相关疾病发作的药物。考虑到这一点，我们筛选了88，000种化学物质，以增加秀丽隐杆线虫线虫的寿命。我们发现米安色林，一种用于人类抗抑郁的5-羟色胺受体拮抗剂，可以增加C。只在成年期注射的话，这种作用会因影响突触处5-羟色胺合成或5-羟色胺再摄取的突变而减弱或消失。它还需要一个血清素受体和一个章鱼胺受体，这两个受体都被药物抑制。米安色林对由于饮食限制或减少食物摄入的突变而延长寿命的动物的寿命没有影响，这表明该药物通过与饮食限制相关的机制延长寿命。这些研究表明，可以通过抑制先前与食物感知有关的某些神经传递来延长寿命，可能是通过模仿与饮食限制相关的生理状态。
One long-term goal of aging research is to find drugs that can delay aging and the onset of age-associated diseases. With this in mind, we screened 88,000 chemicals for the ability to increase the lifespan of Caenorhabditis elegans nematodes. We found that mianserin, a serotonin receptor antagonist used as an antidepressant in humans, can increase C. elegans lifespan when given only during adulthood. This effect is reduced or abolished by mutations that affect serotonin synthesis or serotonin reuptake at synapses. It also requires a serotonin receptor and an octopamine receptor, both of which are inhibited by the drug. Mianserin has no effect on the lifespan of animals with increased longevity due to dietary restriction or with a mutation that reduces food intake, indicating that the drug extends lifespan via mechanisms linked to dietary restriction. These studies indicate that lifespan can be increased by inhibiting certain kinds of neurotransmission previously implicated in food sensing, possibly by mimicking a physiological state associated with dietary restriction.