PDF(Pubmed)
Abstract：
As the most energetically expensive cellular process, translation must be finely tuned to environmental conditions. Dietary restriction attenuates signaling through the nutrient sensing mTOR pathway, which reduces translation and redirects resources to preserve the soma. These responses are associated with increased lifespan but also anabolic impairment, phenotypes also observed when translation is genetically suppressed. Here, we restricted translation downstream of mTOR separately in major tissues in C. elegans to better understand their roles in systemic adaptation and whether consequences to anabolic impairment were separable from positive effects on lifespan. Lowering translation in neurons, hypodermis, or germline tissue led to increased lifespan under well-fed conditions and improved survival upon withdrawal of food, indicating that these are key tissues coordinating enhanced survival when protein synthesis is reduced. Surprisingly, lowering translation in body muscle during development shortened lifespan while accelerating and increasing reproduction, a reversal of phenotypic trade-offs associated with systemic translation suppression. Suppressing mTORC1 selectively in body muscle also increased reproduction while slowing motility during development. In nature, this may be indicative of reduced energy expenditure related to foraging, acting as a \"GO!\" signal for reproduction. Together, results indicate that low translation in different tissues helps direct distinct systemic adaptations and suggest that unknown endocrine signals mediate these responses. Furthermore, mTOR or translation inhibitory therapeutics that target specific tissues may achieve desired interventions to aging without loss of whole-body anabolism.
摘要：
作为最昂贵的细胞过程，翻译必须根据环境条件进行微调。饮食限制减弱通过营养感知mTOR途径的信号传导，这减少了翻译，并重定向了资源以保留soma。这些反应与寿命增加有关，但也与合成代谢障碍有关，当翻译被遗传抑制时也观察到表型。这里,我们在秀丽隐杆线虫的主要组织中分别限制mTOR的下游翻译,以更好地了解它们在系统适应中的作用,以及合成代谢障碍的后果是否与对寿命的积极影响分开.降低神经元的翻译，皮下组织,或种系组织导致在良好喂养条件下的寿命增加，并在撤除食物后提高存活率，表明当蛋白质合成减少时，这些是协调增强存活率的关键组织。令人惊讶的是,在发育过程中降低身体肌肉的翻译缩短了寿命，同时加速和增加了繁殖，与系统性翻译抑制相关的表型权衡的逆转。在身体肌肉中选择性地抑制mTORC1还可以增加生殖，同时减缓发育过程中的运动性。在大自然中,这可能表明与觅食相关的能量消耗减少，充当“GO！”再现信号。一起,结果表明，不同组织中的低翻译有助于指导不同的系统适应，并提示未知的内分泌信号介导这些反应。此外，靶向特定组织的mTOR或翻译抑制治疗剂可以实现对衰老的期望干预而不损失全身合成代谢。
