Journal ArticleDOI
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Matt Kaeberlein,R. Wilson Powers,Kristan K. Steffen,Eric A. Westman,Di Hu,Nick Dang,Emily O. Kerr,Kathryn T. Kirkland,Stanley Fields,Brian K. Kennedy +9 more
TLDR
It is proposed that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast.Abstract:
Calorie restriction increases life span in many organisms, including the budding yeast Saccharomyces cerevisiae . From a large-scale analysis of 564 single-gene–deletion strains of yeast, we identified 10 gene deletions that increase replicative life span. Six of these correspond to genes encoding components of the nutrient-responsive TOR and Sch9 pathways. Calorie restriction of tor1 D or sch9 D cells failed to further increase life span and, like calorie restriction, deletion of either SCH9 or TOR1 increased life span independent of the Sir2 histone deacetylase. We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast.read more
Citations
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mTOR Signaling in Growth Control and Disease
TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
Journal ArticleDOI
mTOR signaling in growth control and disease.
TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
Journal ArticleDOI
TOR signaling in growth and metabolism.
TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
References
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Journal ArticleDOI
Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis
Elizabeth A. Winzeler,Daniel D. Shoemaker,Anna Astromoff,Hong Liang,Keith Anderson,Bruno André,Rhonda Bangham,Rocío Benito,Jef D. Boeke,Howard Bussey,Angela M. Chu,Carla Connelly,Karen Davis,Fred S. Dietrich,Sally Dow,Mohamed El Bakkoury,Françoise Foury,Stephen H. Friend,Erik Gentalen,Guri Giaever,Johannes H. Hegemann,Ted Jones,Michael T. Laub,Hong Liao,Nicole Liebundguth,David J. Lockhart,Anca Lucau-Danila,Marc Lussier,Nasiha M'Rabet,Patrice Menard,Michael Mittmann,Chai Pai,Corinne Rebischung,José L. Revuelta,Linda Riles,Christopher J. Roberts,Petra Ross-Macdonald,Bart Scherens,Michael Snyder,Sharon Sookhai-Mahadeo,Reginald Storms,Steeve Veronneau,Marleen Voet,Guido Volckaert,Teresa R. Ward,Robert W. Wysocki,Grace Yen,Kexin Yu,Katja Zimmermann,Peter Philippsen,Mark Johnston,Ronald W. Davis +51 more
TL;DR: A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome), finding that 17 percent were essential for viability in rich medium.
Journal ArticleDOI
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
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The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
TL;DR: It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.
Journal ArticleDOI
TOR, a Central Controller of Cell Growth
Tobias Schmelzle,Michael N. Hall +1 more
TL;DR: Findings reveal that the target of rapamycin TOR controls an unusually abundant and diverse set of readouts all of which are important for cell growth, suggesting that this conserved kinase is such a central regulator.
Journal ArticleDOI
Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
TL;DR: These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.