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通路调控饮食限制依赖性的寿命延长在 。

pathway regulates dietary restriction-dependent enhancement of lifespan in .

机构信息

RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, India.

Buck Institute for Research on Aging, Novato, United States.

出版信息

Elife. 2021 Jun 8;10:e62621. doi: 10.7554/eLife.62621.

DOI:10.7554/eLife.62621
PMID:34100717
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8233039/
Abstract

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, and mediate the DR response in . Functional characterization of demonstrates its role in neurons while its target 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 , and . Our findings identify 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.

摘要

饮食限制（DR）可延长多种物种的健康寿命。与年龄和营养相关的 microRNAs（miRNAs）及其加工因子丰度的变化与机体的长寿有关。然而，它们调节寿命的机制以及 miRNA 介导的网络在 DR 依赖性延长寿命中的组织特异性作用在很大程度上仍未得到探索。我们表明，两种在神经元中丰富且高度保守的 microRNAs，miR-124 和 miR-132，介导了 中的 DR 反应。对 miR-124 的功能表征表明其在神经元中的作用，而其靶基因 既在神经元中又在脂肪体中发挥作用，以调节脂肪代谢和寿命。蛋白质组学分析表明，Chinmo 通过调节 的表达来发挥其 DR 作用，而 。我们的研究结果表明 是 DR 途径的保守效应因子，并为该小 RNA 分子及其下游效应因子被视为治疗迟发性疾病的潜在药物候选物以及人类健康衰老的生物标志物开辟了道路。

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