Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Colin Selman,Jennifer M. A. Tullet,Daniela Wieser,Elaine E. Irvine,Steven J. Lingard,Agharul I. Choudhury,Marc Claret,Hind Al-Qassab,Danielle Carmignac,Faruk Ramadani,Angela Woods,Iain C. A. F. Robinson,Eugene Schuster,Rachel L. Batterham,Sara C. Kozma,George Thomas,David Carling,Klaus Okkenhaug,Janet M. Thornton,Linda Partridge,David Gems,Dominic J. Withers,Dominic J. Withers +22 more
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TLDR
It is shown 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.Abstract:
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.read more
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
The Hallmarks of Aging
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.
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mTOR Signaling in Growth, Metabolism, and Disease.
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR signaling network contributes to human disease is highlighted.
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mTOR: from growth signal integration to cancer, diabetes and ageing
TL;DR: Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.
Journal ArticleDOI
Extending Healthy Life Span-From Yeast to Humans
TL;DR: Dietary restriction and reduced activity of nutrient-sensing pathways may slow aging by similar mechanisms, which have been conserved during evolution, and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
References
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison,Randy Strong,Zelton D Sharp,James F. Nelson,Clinton M. Astle,Kevin Flurkey,Nancy L. Nadon,J. Erby Wilkinson,Krystyna Frenkel,Christy S. Carter,Christy S. Carter,Marco Pahor,Marco Pahor,Martin A. Javors,Elizabeth Fernandez,Richard A. Miller +15 more
TL;DR: It is reported that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.
Journal ArticleDOI
AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity
Carles Cantó,Zachary Gerhart-Hines,Jerome N. Feige,Marie Lagouge,Liliana Noriega,Liliana Noriega,Jill C. Milne,Peter J. Elliott,Pere Puigserver,Johan Auwerx,Johan Auwerx +10 more
TL;DR: It is demonstrated that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD+-dependent type III deacetylase SIRT1.
Journal ArticleDOI
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Martin Holzenberger,Joëlle Dupont,Bertrand Ducos,Patricia Leneuve,Alain Géloën,Patrick C. Even,Pascale Cervera,Yves Le Bouc +7 more
TL;DR: Results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan, and shows greater resistance to oxidative stress.
Journal ArticleDOI
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Sung Hee Um,Francesca Frigerio,Mitsuhiro Watanabe,Frédéric Picard,Manel Joaquin,Melanie Sticker,Stefano Fumagalli,Peter R. Allegrini,Sara C. Kozma,Sara C. Kozma,Johan Auwerx,George Thomas +11 more
TL;DR: It is reported that S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation, however on a high fat diet, levels of glucose and free fatty acids still rise in S6k1- deficient mice, resulting in insulin receptor desensitization.