The upper-airway microbiota and loss of asthma control among asthmatic children.
The upper-airway microbiota and loss of asthma control among asthmatic children.
复制标题
衰老过程中，分泌的 microRNA 会破坏秀丽隐杆线虫不同组织中的自噬
DOI：
10.1038/s41467-019-12821-2
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发表时间：
2019-01-01
影响因子：
16.6
通讯作者：
Wanda Phipatanakul
中科院分区：
文献类型：
--
作者：
Zhou, Yan-jiao;Jackson, Daniel;Wanda Phipatanakul
宏自噬是蛋白质质量控制中的一个关键因素，被认为在不同的组织中受到系统性的损害，并导致整个身体的蛋白质稳态和衰老的协调破坏。虽然自噬和衰老的组织特异性变化已经被广泛探索，但组织间调节自噬与衰老的机制却知之甚少。在这里，我们证明了一个分泌的microRNA，mir-83/miR-29，控制了秀丽线虫组织中与年龄相关的宏观自噬的减少。随着年龄的增长，HSF-1/HSF1在肠道中上调，mir-83可能通过细胞外小泡跨组织运输，并通过抑制肠道内和体壁肌肉中的非自主自噬调节因子CUP-5/MCOLN来扰乱宏观自噬。因此，突变的mir-83增强了不同组织中的宏观自噬，促进了蛋白质的动态平衡和寿命。因此，这些发现确定了一种基于microRNA的机制，以协调不同组织中随年龄减少的巨型自噬。
Macroautophagy, a key player in protein quality control, is proposed to be systematically impaired in distinct tissues and causes coordinated disruption of protein homeostasis and ageing throughout the body. Although tissue-specific changes in autophagy and ageing have been extensively explored, the mechanism underlying the inter-tissue regulation of autophagy with ageing is poorly understood. Here, we show that a secreted microRNA, mir-83/miR-29, controls the age-related decrease in macroautophagy across tissues in Caenorhabditis elegans. Upregulated in the intestine by hsf-1/HSF1 with age, mir-83 is transported across tissues potentially via extracellular vesicles and disrupts macroautophagy by suppressing CUP-5/MCOLN, a vital autophagy regulator, autonomously in the intestine as well as non-autonomously in body wall muscle. Mutating mir-83 thereby enhances macroautophagy in different tissues, promoting protein homeostasis and longevity. These findings thus identify a microRNA-based mechanism to coordinate the decreasing macroautophagy in various tissues with age.