Patent
Compositions for manipulating the lifespan and stress response of cells and organisms
TLDR
In this article, methods and compositions for modulating the activity of sirtuin deacetylase protein family members are presented, including p53 activity; apoptosis; lifespan and sensitivity to stress of cells and organisms.Abstract:
Provided herein are methods and compositions for modulating the activity of sirtuin deacetylase protein family members; p53 activity; apoptosis; lifespan and sensitivity to stress of cells and organisms. Exemplary methods comprise contacting a cell with an activating compound, such as a flavone, stilbene, flavanone, isoflavone, catechin, chalcone, tannin or anthocyanidin; or an inhibitory compound, such as a sphingolipid, e.g., sphingosine.read more
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Patent
Method for altering the lifespan of eukaryotic organisms
TL;DR: In this paper, a method for altering the lifespan of a eukaryotic organism was proposed, which comprises the steps of providing a lifespan altering compound, and administering an effective amount of the compound to the organism, such that the organism is altered.
Patent
Neural stimulation devices and systems for treatment of chronic inflammation
TL;DR: In this article, a system for treating chronic inflammation may include an implantable micro-stimulator, a wearable charger, and optionally an external controller, which can address several types of stimulation including regular dose delivery.
Patent
Nerve cuff with pocket for leadless stimulator
TL;DR: An extravascular nerve cuff that is configured to hold a leadless, integral, implantable microstimulator is described in this paper, where the nerve cuff can be secured around the nerve such that the electrodes of the device are stably positioned relative to the nerve.
Patent
Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders
TL;DR: In this article, methods and compositions for treating or preventing metabolic disorders, such as obesity and diabetes, are presented. Methods may comprise modulating the activity or level of a sirtuin, such a SIRTl or Sir2.
Patent
Compositions for treating or preventing obesity and insulin resistance disorders
TL;DR: In this article, methods and compositions for modulating the activity or level of a sirtuin, thereby treating or preventing obesity or an insulin resistance disorder, such as diabetes in a subject, are presented.
References
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Journal ArticleDOI
Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
Journal ArticleDOI
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.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Homayoun Vaziri,Scott K. Dessain,Scott K. Dessain,Elinor Ng Eaton,Shin-ichiro Imai,Roy A. Frye,Tej K. Pandita,Leonard Guarente,Robert A. Weinberg +8 more
TL;DR: It is proposed that hSir2, the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue.