The mechanistic Target of Rapamycin: The grand conducTOR of metabolism and aging
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TLDR
The molecular basis for the negative metabolic side effects associated withRapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism, are discussed.About:
This article is published in Cell Metabolism.The article was published on 2016-06-14 and is currently open access. It has received 406 citations till now. The article focuses on the topics: Mechanistic target of rapamycin & RPTOR.read more
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In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming
Alejandro Ocampo,Pradeep Reddy,Paloma Martinez-Redondo,Aida Platero-Luengo,Fumiyuki Hatanaka,Tomoaki Hishida,Mo Li,David Lam,Masakazu Kurita,Masakazu Kurita,Ergin Beyret,Toshikazu Araoka,Toshikazu Araoka,Eric Vazquez-Ferrer,David Donoso,Jose Luis Roman,Jinna Xu,Concepcion Rodriguez Esteban,Gabriel Núñez,Estrella Nuñez Delicado,Josep M. Campistol,Isabel Guillen,Pedro Guillen,Juan Carlos Izpisua Belmonte +23 more
TL;DR: It is reported that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging.
Journal ArticleDOI
Autophagy as a promoter of longevity: insights from model organisms
TL;DR: Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, Autophagy supports tissue and organismal fitness and promotes longevity.
mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and Rapamycin
Seong A. Kang,Michael E. Pacold,Christopher L. Cervantes,Daniel Lim,Hua Jane Lou,Kathleen Ottina,Nathanael S. Gray,Benjamin E. Turk,Michael B. Yaffe,Michael B. Yaffe,David M. Sabatini +10 more
TL;DR: The hypothesis is that differences in substrate quality are one mechanism for allowing downstream effectors of mTORC1 to respond differentially to temporal and intensity changes in the levels of nutrients and growth factors as well as pharmacological inhibitors such as rapamycin.
Journal ArticleDOI
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease.
TL;DR: The breadth and depth of metabolic flexibility and its impact on health and disease are discussed and important advances in metabolic flexibility research are outlined and medical horizons and translational aspects are outlined.
A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity
David M. Sabatini,Brian C. Grabiner,Valentina Nardi,Kıvanç Birsoy,Richard Possemato,Kuang Shen,Sumi Sinha,Alexander Jordan,Andrew H. Beck +8 more
TL;DR: In this paper, a comprehensive catalog of mTOR pathway mutations in cancer was generated using publicly available tumor genome sequencing data, identifying 33 mutations in the C-terminal half of the mTOR kinase.
References
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PatentDOI
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.
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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.
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TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
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Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
Dos D. Sarbassov,Siraj M. Ali,Do Hyung Kim,David A. Guertin,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is found that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.
Journal ArticleDOI
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Yasemin Sancak,Timothy R. Peterson,Yoav D. Shaul,Robert A. Lindquist,Carson C. Thoreen,Liron Bar-Peled,David M. Sabatini,David M. Sabatini +7 more
TL;DR: It is found that the Rag proteins—a family of four related small guanosine triphosphatases (GTPases)—interact with mTORC1 in an amino acid–sensitive manner and are necessary for the activation of the m TORC1 pathway by amino acids.