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首页> 外文期刊>International Journal of Molecular Sciences >Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation
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Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

机译：牛奶-促进mTORC1依赖性翻译的哺乳动物进化营养系统。

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Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases.
机译：基于对人类食用牛奶的生物化学和激素作用的翻译研究，该文献提出牛奶是哺乳动物进化的信号系统，它激活了雷帕霉素复合物1（mTORC1）的营养敏感激酶机制靶标，该靶标是雷帕霉素复合物的关键调节剂。翻译。乳汁是一种乳腺来源的分泌产物，对于特定种类的基因-营养相互作用而言是必需的，以促进新生哺乳动物的适当生长和发育。该信号系统高度保守，受泌乳基因组严格控制。牛奶足以激活mTORC1，mTORC1是蛋白质，脂质和核苷酸合成的关键调节剂，负责合成代谢，细胞生长和增殖。为了实现其mTORC1激活功能，牛奶提供了四个关键的代谢信使：（1）必需的支链氨基酸（BCAA）; （2）谷氨酰胺; （3）棕榈酸; （4）具有生物活性的外泌体microRNA，它们以协同方式促进mTORC1依赖性翻译。在除了新石器时代的人类以外的所有哺乳动物中，牛奶摄入对mTORC1的产后激活仅限于产后哺乳期。至关重要的问题是，mTORC1的持续过度活化与衰老和与年龄相关的疾病（例如肥胖症，2型糖尿病，癌症和神经退行性疾病）的发展有关。持续的mTORC1激活可促进内质网（ER）应激，并驱动无目标的准程序，从而促进衰老和与年龄有关的疾病。

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