核糖体蛋白S6激酶1信号通路调节哺乳动物寿命。
Ribosomal protein S6 kinase 1 signaling regulates mammalian life span.
作者信息
Selman Colin, Tullet Jennifer M A, Wieser Daniela, Irvine Elaine, Lingard Steven J, Choudhury Agharul I, Claret Marc, Al-Qassab Hind, Carmignac Danielle, Ramadani Faruk, Woods Angela, Robinson Iain C A, Schuster Eugene, Batterham Rachel L, Kozma Sara C, Thomas George, Carling David, Okkenhaug Klaus, Thornton Janet M, Partridge Linda, Gems David, Withers Dominic J
机构信息
Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK.
出版信息
Science. 2009 Oct 2;326(5949):140-4. doi: 10.1126/science.1177221.
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.
热量限制（CR）可预防衰老和疾病，但其影响哺乳动物寿命的机制尚不清楚。我们在小鼠中发现，核糖体S6蛋白激酶1（S6K1）缺失，营养反应性mTOR（雷帕霉素哺乳动物靶标）信号通路的一个组成部分，导致寿命延长，并对与年龄相关的病理状况产生抗性，如骨骼、免疫和运动功能障碍以及胰岛素敏感性丧失。S6K1缺失诱导的基因表达模式类似于在热量限制或用腺苷单磷酸（AMP）激活的蛋白激酶（AMPK）进行药理学激活时所观察到的模式，AMPK是对热量限制的代谢反应的保守调节因子。我们的结果表明，S6K1影响健康的哺乳动物寿命，并表明对S6K1和AMPK的治疗性操作可能模拟热量限制，并可为衰老相关疾病提供广泛的保护。
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