Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan.
Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan.
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DOI：
10.1371/journal.pgen.1003737
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发表时间：
2013-08
期刊：
影响因子：
4.5
通讯作者：
Driscoll M
中科院分区：
文献类型：
--
作者：
Vora M;Shah M;Ostafi S;Onken B;Xue J;Ni JZ;Gu S;Driscoll M
热量/饮食限制（CR/DR）可以促进长寿，并防止跨物种的年龄相关疾病。因此，协调食物摄入与健康促进代谢的分子机制具有重要的医学意义。我们报告保守的秀丽隐杆线虫microRNA-80（mir-80）是DR状态的主要调节因子。mir-80缺失赋予全系统的健康衰老，包括在高龄时维持心脏样和骨骼肌样功能，减少脂褐素的积累，以及延长寿命，与DR的生理特征的诱导一致。mir-80表达通常在随意进食下高而在食物限制下低，在后肠中具有最显著的食物敏感性表达变化。乙酰转移酶转录辅因子cbp-1、相互作用转录因子daf-16/FOXO和热休克因子-1 hsf-1对于mir-80（Δ）的益处至关重要。cbp-1转录物中的候选miR-80靶序列可能赋予食物依赖性调节。在食物限制下，降低的miR-80水平直接或间接增加CBP-1蛋白水平，以参与促进DR的代谢循环。饮食限制，限制卡路里摄入，维持维生素和矿物质支持，可以延长寿命，并防止许多物种的老年疾病。因此，在简单的动物模型中控制饮食限制的分子机制的建立可以为激活促进健康的代谢的策略提供信息，以帮助解决与衰老和年龄相关疾病相关的临床挑战。我们描述了一个单一的秀丽隐杆线虫microRNA基因，保持饮食限制计划时，食物丰富。mir-80缺失表现出饮食限制的有益特征，无论食物的可用性如何，包括在生命后期延长维持活动性和心脏样肌肉功能以及延长寿命。我们确定了这些益处所需的三个关键长寿基因。我们假设miR-80是一个核心调节因子，通过它协调调节多种和交叉的代谢途径以响应营养物质的可用性。
Caloric/dietary restriction (CR/DR) can promote longevity and protect against age-associated disease across species. The molecular mechanisms coordinating food intake with health-promoting metabolism are thus of significant medical interest. We report that conserved Caenorhabditis elegans microRNA-80 (mir-80) is a major regulator of the DR state. mir-80 deletion confers system-wide healthy aging, including maintained cardiac-like and skeletal muscle-like function at advanced age, reduced accumulation of lipofuscin, and extended lifespan, coincident with induction of physiological features of DR. mir-80 expression is generally high under ad lib feeding and low under food limitation, with most striking food-sensitive expression changes in posterior intestine. The acetyltransferase transcription co-factor cbp-1 and interacting transcription factors daf-16/FOXO and heat shock factor-1 hsf-1 are essential for mir-80(Δ) benefits. Candidate miR-80 target sequences within the cbp-1 transcript may confer food-dependent regulation. Under food limitation, lowered miR-80 levels directly or indirectly increase CBP-1 protein levels to engage metabolic loops that promote DR. Dietary restriction, limitation of calorie intake with maintained vitamin and mineral support, can extend lifespan and protect against diseases of age across many species. Elaboration of molecular mechanisms that control dietary restriction in simple animal models may therefore inform on strategies to activate health-promoting metabolism to help address clinical challenges associated with aging and age-associated disease. We characterize a single Caenorhabditis elegans microRNA gene that keeps dietary restriction programs off when food is abundant. A mir-80 deletion exhibits beneficial features of dietary restriction regardless of food availability, including extended maintenance of mobility and cardiac-like muscle function later into life as well as lifespan extension. We identify three key longevity genes that are required for these benefits. We hypothesize that miR-80 is a core regulator by which diverse and intersecting metabolic pathways are coordinately regulated to respond to nutrient availability.
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影响因子：
7.8
作者：
Kaeberlein, Tammi L.;Smith, Erica D.;Kaeberlein, Matt
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0400848101
发表时间：
2004-05-25
影响因子：
11.1
作者：
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通讯作者：
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通讯作者：
Driscoll, M