Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of Drosophila subjected to DR or low TOR and predict regulatory TFs. We predict and validate roles for the evolutionarily conserved GATA family of TFs, and identify conservation of this signal in mice. Importantly, restricting knockdown of the GATA TF srp to specific fly tissues recapitulated the benefits but not the costs of DR. Together, our data indicate that the GATA TFs mediate effects of dietary amino acids on lifespan, and that by manipulating them in specific tissues it is possible to reap the fitness benefits of EAAs, decoupled from a cost to longevity.

饮食限制（DR）可以延长动物的寿命，但会增加健身成本。这种现象取决于饮食中的必需氨基酸（EAA）和TOR信号传导，它们会发挥全身作用。但是，在DR表型的各个方面，特定组织和细胞自主转录调节因子的作用尚不清楚。专门在限制寿命的组织中操作相关的转录因子（TF）可能会使DR的寿命受益与早期健身成本分开。在这里，我们系统地分析果蝇在经历DR或低TOR的器官之间的转录，并预测调节性TF。我们预测并验证进化上保守的GATA家族的作用，并确定该信号在小鼠中的保守性。重要的是，限制GATA TF的组合对特定果蝇组织的srp概括了DR的益处，但没有概括其成本。总之，我们的数据表明，GATA TF介导了膳食氨基酸对寿命的影响，并且通过在特定组织中进行操作，有可能获得EAA的健身益处，而成本与寿命却不相关。