miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila.
miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila.
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DOI：
10.7554/elife.62621
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发表时间：
2021-06-08
期刊：
影响因子：
7.7
通讯作者：
Chawla G
中科院分区：
文献类型：
--
作者：
Pandey M;Bansal S;Bar S;Yadav AK;Sokol NS;Tennessen JM;Kapahi P;Chawla G
饮食限制（DR）延长了不同物种的健康寿命。年龄和营养相关的microRNA（miRNAs）及其加工因子丰度的变化与生物体寿命有关。然而，它们调节寿命的机制以及miRNA介导的网络在DR依赖性寿命增强中的组织特异性作用仍然在很大程度上未被探索。我们发现，两个神经富集和高度保守的microRNA，miR-125和let-7介导的DR反应在果蝇。miR-125的功能表征表明其在神经元中的作用，而其靶点chinmo在神经元和脂肪体中均起作用，以调节脂肪代谢和寿命。蛋白质组学分析表明，Chinmo通过调节FATP，CG 2017，CG 9577，CG 17554，CG 5009，CG 8778，CG 9527和FASN 1的表达来发挥其DR效应。我们的发现将miR-125确定为DR通路的保守效应子，并为这种小RNA分子及其下游效应子开辟了途径，被认为是治疗晚发型疾病的潜在候选药物和人类健康衰老的生物标志物。
Dietary restriction (DR) extends healthy lifespan in diverse species. Age and nutrient-related changes in the abundance of microRNAs (miRNAs) and their processing factors have been linked to organismal longevity. However, the mechanisms by which they modulate lifespan and the tissue-specific role of miRNA-mediated networks in DR-dependent enhancement of lifespan remains largely unexplored. We show that two neuronally enriched and highly conserved microRNAs, miR-125 and let-7 mediate the DR response in Drosophila melanogaster. Functional characterization of miR-125 demonstrates its role in neurons while its target chinmo acts both in neurons and the fat body to modulate fat metabolism and longevity. Proteomic analysis revealed that Chinmo exerts its DR effects by regulating the expression of FATP, CG2017, CG9577, CG17554, CG5009, CG8778, CG9527, and FASN1. Our findings identify miR-125 as a conserved effector of the DR pathway and open the avenue for this small RNA molecule and its downstream effectors to be considered as potential drug candidates for the treatment of late-onset diseases and biomarkers for healthy aging in humans.