Comparative transcriptional profiling identifies takeout as a gene that regulates life span.

Comparative transcriptional profiling identifies takeout as a gene that regulates life span.
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DOI:
10.18632/aging.100146
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发表时间:
2010-05
期刊:
Aging
影响因子:
--
通讯作者:
Helfand SL
Helfand SL
中科院分区:
其他
文献类型:
--
作者:
Bauer J;Antosh M;Chang C;Schorl C;Kolli S;Neretti N;Helfand SL

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翻译积极的一个主要挑战是 饮食限制(DR)对改善人类健康的作用是 治疗模拟物的发展。 寻找DR模拟的一种方法 基于DR寿命的近端效应器的识别 扩展名.果蝇DR的全基因组分析显示, 许多基因表达的变化,使其难以建立 与其他变化相比, 无关的生理变化。我们使用比较全基因组表达 分析以发现其表达变化在DR之间共享的基因, 以及两种与DR相关的分子遗传寿命延长干预, 增加dSir 2和降低Dmp 53活性。我们发现了二十一个基因 三种相关的延长寿命干预措施之间存在共同点。 之一 这些被认为与昼夜节律、进食行为和保幼激素结合有关的基因takeout也在四种其他延长寿命的条件下增加:Rpd3, 印地、奇科和玛士撒拉。 我们展示外卖 通过增加成年人的外卖, 表达和延长寿命。这些研究表明, 比较全基因组转录谱用于鉴定特异性 DR寿命延长途径的下游元件。
A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway.
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