【原】核糖体蛋白S6激酶1信号调节哺乳动物的寿命

Ribosomal protein S6 kinase 1 signaling regulates mammalian life span.

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|核心内容：

卡路里限制(CR)可以预防衰老和疾病，但其影响哺乳动物寿命的机制尚不清楚。

Fig. 1. Extended lifespan of mice with deletion of S6K1 -/-

我们在小鼠中发现，作为营养反应mTOR(哺乳动物雷帕霉素靶标)信号通路的一部分，核糖体S6蛋白激酶1(S6K1)的缺失导致寿命延长，并对与年龄相关的疾病(如骨骼、免疫、运动功能障碍和胰岛素敏感性丧失)产生抵抗力。

Fig. 2. Age-related pathology and physiological characteristics of 600 day old female S6K1 -/- mice

S6K1缺失诱导的基因表达模式与CR相似，或药物激活一磷酸腺苷(AMP)激活的蛋白激酶(AMPK)，AMPK是对CR的代谢反应的保守调节因子。

Fig. 3. Enhanced AMPK activation by AICAR of S6K1 -/- hepatocytes, increased AAK-2 phosphorylation in rsks-1(ok1255) mutants and effects of loss of aak-2(ok524) on longevity and physiology.

我们的结果表明，S6K1影响健康哺乳动物的寿命，提示S6K1和AMPK的治疗操作可能模仿CR，对衰老疾病提供广泛的保护。

原文摘要：

Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

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参考文献：http:///backend/ptpmcrender.fcgi?accid=PMC4954603&blobtype=pdf

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