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Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators
Basil P. Hubbard,Ana P. Gomes,Han Dai,Jun Li,April Case,Thomas Considine,Thomas V. Riera,Jessica E. Lee,E. Sook Yen,Dudley W. Lamming,Eli Schuman,Linda Stevens,Alvin J. Y. Ling,Sean M. Armour,Shaday Michan,Huizhen Zhao,Yong Jiang,Sharon Sweitzer,Charles A. Blum,Jeremy S. Disch,Pui Yee Ng,Konrad T. Howitz,Anabela P. Rolo,Yoshitomo Hamuro,Joel Moss,Robert B. Perni,James L. Ellis,George P. Vlasuk,David A. Sinclair,Bradley L. Pentelute +29 more
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TLDR
Yuan et al. as mentioned in this paper found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT 1 activation by STACs.Abstract:
It's a SIRT Intense attention has focused on the SIRT1 deacetylase as a possible target for anti-aging drugs. But unexpected complications in assays of SIRT1 activity have made it unclear whether compounds thought to be sirtuin-activating compounds (STACs) are really direct regulators of the enzyme. Further exploration of these effects by Hubbard et al. (p. 1216; see the Perspective by Yuan and Marmorstein) revealed that interaction of SIRT1 with certain substrates allows activation of SIRT1 by STACs and identified critical amino acids in SIRT1 required for these effects. Mouse myoblasts reconstituted with SIRT1 mutated at this amino acid lost their responsiveness to STACs. An interaction of the deacetylase SIRT1 with its substrate offers a possible explanation for some effects on aging. [Also see Perspective by Yuan and Marmorstein] A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu230, located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.read more
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Je älter, desto besser — Hefe als Modell — system für die Alterungsforschung
TL;DR: Yeast will remain as a major workhorse for aging research in the post-genome era, especially for the search for aging modulators and for the system biology of aging.
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Endothelial SIRT-1 has a critical role in the maintenance of capillarization in brown adipose tissue
Ryo Furuuchi,Ippei Shimizu,Yohko Yoshida,Goro Katsuumi,Masayoshi Suda,Yoshiaki Kubota,K. Walsh,Tohru Minamino +7 more
TL;DR: In this paper , the role of Boysenberry polyphenols (BoyP) in BAT has been investigated, and BoyP decreased EC apoptosis, enhanced capillarization, and ameliorated dietary BAT dysfunction, which was associated with the upregulation of nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin 1 (SIRT-1) in ECs.
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SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae))
TL;DR: SIRT1 is a member of the mammalian sirtuin genes that encode for seven protein lysine modifiers with deacetylase, ADP-ribosyltransferase and other deacylase activities that plays diverse roles in regulating cell proliferation, differentiation, stress response, metabolism, energy homeostasis, aging and cancer.
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Transcription Factors as Targets of Natural Compounds in Age-Related Diseases and Cancer: Potential Therapeutic Applications
TL;DR: In this paper , the accumulation of SIRT1-, NF-κB-, and FoxO-mediated inflammatory processes and cellular pro-inflammatory signaling pathways is described. And the proinflammatory mechanisms underlying metabolic molecular pathways in various diseases such as liver cancer and diabetes are highlighted.
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Resveratrol reverses male reproductive damage in rats exposed to nicotine during the intrauterine phase and breastfeeding
Camila Monteiro Francisco,L. Fischer,Vanessa Vendramini,Samara Urban de Oliva,Camila Cicconi Paccola,Sandra Maria Miraglia +5 more
TL;DR: Resveratrol, a polyphenol, is a biological modulator that can positively act on male reproduction, and its expression can be affected by nicotine and modulated by resver atrol.
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.
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Resveratrol improves health and survival of mice on a high-calorie diet
Joseph A. Baur,Kevin J. Pearson,Nathaniel O Price,Hamish A. Jamieson,Carles Lerin,Avash Kalra,Vinayakumar Prabhu,Joanne S. Allard,Guillermo López-Lluch,Kaitlyn N. Lewis,Paul J. Pistell,Suresh Poosala,Kevin G. Becker,Olivier Boss,Dana M. Gwinn,Mingyi Wang,Sharan Ramaswamy,Kenneth W. Fishbein,Richard G. Spencer,Edward G. Lakatta,David G. Le Couteur,Reuben J. Shaw,Plácido Navas,Pere Puigserver,Donald K. Ingram,Rafael de Cabo,David A. Sinclair +26 more
TL;DR: It is shown that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice onA standard diet and significantly increases their survival and point to new approaches for treating obesity-related disorders and diseases of ageing.
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Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Konrad T. Howitz,Kevin J. Bitterman,Haim Y. Cohen,Dudley W. Lamming,Siva Lavu,Jason G. Wood,Robert E. Zipkin,Phuong Chung,Anne Kisielewski,Li-Li Zhang,Brandy Scherer,David A. Sinclair +11 more
TL;DR: The potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating Sirt1-dependent deacetylation of p53.
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Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase
Anne Brunet,Lora B. Sweeney,J. Fitzhugh Sturgill,Katrin F. Chua,Paul L. Greer,Yingxi Lin,Hien Tran,Sarah E. Ross,Raul Mostoslavsky,Haim Y. Cohen,Linda Hu,Hwei-Ling Cheng,Mark P. Jedrychowski,Steven P. Gygi,David A. Sinclair,Frederick W. Alt,Michael E. Greenberg +16 more
TL;DR: One way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.
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Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.
Joseph T. Rodgers,Carlos Lerin,Wilhelm Haas,Steven P. Gygi,Bruce M. Spiegelman,Pere Puigserver +5 more
TL;DR: It is shown that the Sir2 homologue, SIRT1 controls the gluconeogenic/glycolytic pathways in liver in response to fasting signals through the transcriptional coactivator PGC-1α, and this findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan.