97 results about "Sirtuin" patented technology

The invention relates to the induction of apoptosis by inhibition of the sirtuin SIRT1 expression, in particular the induction of apoptosis in tumour cells. Materials and methods for inhibiting SIRT1 expression are provided, including RNA interference methods. In particular, the invention provides a method of treating a proliferative disease comprising administering to an individual in need thereof an effective amount of a SIRT1 inhibitor.

Sirtuin modulators, particularly sirtuin activators, are useful in treating vision impairment. In general, the sirtuin modulators inhibit the progression of vision impairment resulting from various eye disorders. The invention also includes pharmaceutically acceptable formulations of sirtuin modulators, particular ophthalmically acceptable formulations.

Sirtuin modulators, particularly sirtuin activators, are useful in treating vision impairment. In general, the sirtuin modulators inhibit the progression of vision impairment resulting from various eye disorders. The invention also includes pharmaceutically acceptable formulations of sirtuin modulators, particular ophthalmically acceptable formulations.

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions can contain synergizing amounts of a sirtuin-pathway activators, including but not limited to resveratrol, in combination with beta-hydroxymethylbutyrate (HMB), keto isocaproic acid (KIC), leucine, or combinations of HMB, KIC and leucine.

An agent for treating various kinds of diseases which contains at least one selected from the group consisting of sexual steroid hormone such as estrogen or its metabolites, its derivative, structural analogues thereof, estrogen acting substance or SERM non-feminizing estrogen (non-hormonal estrogen), and an activator of sirtuin and has a form of eye drops or eye washes, oral preparation, etc. An agent for treating eye diseases which has excellent treatment effects, reduced in side action can be provided.

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions can contain synergizing amounts of a sirtuin-pathway activators, including but not limited to resveratrol, in combination with beta-hydroxymethylbutyrate (HMB), keto isocaproic acid (KIC), leucine, or combinations of HMB, KIC and leucine.

Systems, devices and methods for modulation of sirtuins by neurostimulation. In particular, sirtuins may be modulated by stimulation of the vagus nerve. Further described herein generally are methods, systems and devices, for specifically modulating sirtuins, including sub-sets (types or localized regions) of sirtuins by vagus nerve stimulation (VNS).

The present invention relates to sirtuin 6 activating peptides, derived from highly conserved regions of human SIRT proteins, and to a cosmetic or pharmaceutical composition comprising at least one sirtuin 6 activating peptide in a physiologically acceptable medium. The invention further relates to the utilization of a cosmetic composition to prevent and / or repair DNA degradation, improve telomere maintenance and reduce cellular senescence. The invention also applies to a cosmetic treatment process intended to prevent and / or treat the cutaneous signs of aging and photo aging.

Methods useful for reducing or preventing non-alcoholic steatohepatitis or hepatic steatosis are provided herein. Such methods may comprise administering to a subject in need thereof a sirtuin pathway activator and / or PDE5 inhibitor alone or in combination with an amount of a branched amino acid in free amino acid form, or a metabolite thereof. Also provided herein are compositions and kits for practicing any of the methods described herein.

The identification and cloning of histone deacetylase 9 (HDAC9) is disclosed, and in particular full length HCAC9 polypeptides and HDAC9 polypeptides which have deacetylase activity, and to nucleic acid molecules encoding these polypeptides. The uses of these polypeptides and nucleic acid molecules are disclosed, for example for screening for compounds that are capable of modulating HDAC9 biological activity.

The present invention relates to compounds which activate the p53 response, and find use in, for example, hyperproliferative diseases such as cancer treatment and potentially other diseases / conditions (involving sirtuin function).

The invention relates to the use of sirtuin inhibitors for reducing TNF-alpha production by cells and organisms. The invention also concerns prophylactic and therapeutic applications of sirtuin inhibitors in TNF-alpha mediated pathologies, such as various inflammatory and autoimmune disorders.

The present invention provides for systems, compositions, methods and kits for regulating energy metabolism in pets. The systems, compositions, and kits can comprise, and methods can make use of, pet foods, pet treats, pet supplements, and pet drinks. In one aspect, the invention provides for pet food, treat, supplement, and drink compositions that comprise a combination of (a) leucine, and (b) a sirtuin activator, or any precursors or metabolites of (a) or (b). These combinations may be effective for reducing weight or adipose volume in the pet. In another aspect, the invention provides for methods of regulating energy metabolism by the administration of one or more compositions comprising leucine, a leucine metabolite, and / or a sirtuin activator. The invention also provides for kits comprising compositions of leucine, a leucine metabolite, and / or a sirtuin activator packaged in an oral dose form with usage instructions.

A cannabis-based flavonoid pharmaceutical composition including any one or more selected from among the group of Cannflavin A, Cannflavin B. Cannflavin C, Chrysoeriol, Cosmosiin, Flavocannabiside and their derivatives selected from among the group of Geraldol, Rhamnetin, Isorhamnetin, Rhamnazin, or their synthases, for the prevention and treatment of certain cancers that can be treated by therapeutically targeting oncogenic factors including kinases, sirtuins, bromodomains, matrix metalloproteinases and histone acetylases. Some of the cancers that can be treated by use of cannabis flavonoids based on the inhibition of these therapeutic targets include but are not limited to brain, breast, colon, renal liver, lung, pancreatic, pigmented villonodular synovitis, prostate, leukemia, melanomam, tenosynovial giant cell tumor, as well as any other cancers that overexpress the oncogenic factors inhibited, by the cannabis flavonoids or their derivatives herein identified.

A method for determining protein binding specificity using a screen of a peptide library is provided. The method can be used to determine binding specificity for human NAD+-dependent deacetylase SIRT1, and to identify the most efficiently deacetylated peptide sequences. The method can be also used to screen a combinatorial H4 histone N-terminal tail peptide library to examine the binding preferences of a alpha-phos (S1) H4 antibody toward all known possible H4 histone modification states.

The present invention includes methods for preparing resveratrol, resveratrol esters and substituted and unsubstituted stilbenes of the formula given below; where each Y is —O or halogen, each Z is —O or halogen, each n and each m is independently the value of 0, 1, 2, 3, 4 or 5, each A and each B is independently selected from Pn, R or absent, each V and each W is independently selected from Pn, straight or branched alkyl of from (2) to (6) carbon atoms and cycloalkyl of from (3) to (8) carbon atoms, alkoxy, phenyl, benzyl or halogen, R is independently selected from the group comprising alkyl with at least one carbon atom, aryl and aralkyl, Pn is an alcohol protecting group and diastereoisomers of the foregoing. The compounds are made from a multi-step process including a N-heterocyclic carbon-type ligand coupling in the presence of a base with benzyol halide and styrene coupling partners. These compounds show increased stability for use in the food, cosmetic and pharmaceutical industries.

The present invention relates to a method for identifying compounds that modulate the activity of sirtuin deacetylase protein family members. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified nicotinamide inhibition and base exchange site of Sir2 and testing the compound for its ability to modulate the activity of the Sir2 protein. Compositions and methods for preventing or treating diseases or disorders associated with Sir2 are also provided.

Methods useful for sustaining a reduction of non-alcoholic steatohepatitis are provided herein. Such methods may comprise administering to a subject in need thereof a sirtuin pathway activator and / or PDE5 inhibitor alone or in combination with an amount of a branched amino acid in free amino acid form, or a metabolite thereof. Also provided herein are compositions and kits for practicing any of the methods described herein.

The present invention provides treatment methods involving modulating a sirtuin activity and / or a sirtuin mRNA and / or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and / or SIRT mRNA and / or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and / or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide. The present invention further provides active agents that modulate sirtuin activity or expression; and compositions, including pharmaceutical compositions, comprising the active agents.

The invention encompasses compositions and methods for effectively treating and / or preventing osteoporosis and related disorders such as osteoarthritis and rheumatoid arthritis, and for promoting overall bone and joint health. This is accomplished by totally addressing the multiple mechanisms that lead to such disorders. The invention includes compositions comprising a combination of agents that effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that increase the risk for development of osteoporosis. The present compositions and methods simultaneously promote bone formation and reduce bone resorption by (a) stimulating osteoblast formation and osteogenesis; (b) suppressing adipocyte differentiation; (c) inhibiting osteoclast formation; and (d) increasing apoptosis of osteoclasts. The inventive compositions used for administration to human and other mammalian subjects having or at risk for development of osteoporosis comprise (1) at least one agent capable of modulating expression and / or activity of one or more of peroxisome activated protein receptor gamma (PPAR-γ), CAAT / enhancer binding protein-α (C / EBPα) and Sterol Regulatory Element-Binding Protein (SREBP-1); (2) at least one agent that activates expression and / or activity of one or more of the osteogenic transcription factors (Runx2 / Cbfα1, Dlx5, Osterix, Msx2); (3) at least one agent that activates expression and / or activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4), alkaline phosphatase (ALP), and osteocalcin; (4) at least one agent capable of activating Wnt / β-catenin signaling pathway; (5) at least one agent that inhibits the activity of pro-oxidants including reactive nitrogen species and reactive oxygen species (ROS); (6) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2); and (7) at least one agent that induces the expression of and / or activates one or more of adenosine monophosphate-activated protein kinase (AMPK), sirtuin (SIRT1) and adiponectin (AP).

The invention relates to the induction of apoptosis by inhibition of the sirtuin SIRT1 expression, in particular the induction of apoptosis in tumour cells. Materials and methods for inhibiting SIRT1 expression are provided, including RNA interference methods. In particular, the invention provides a method of treating a proliferative disease comprising administering to an individual in need thereof an effective amount of a SIRT1 inhibitor.

The present invention provides treatment methods involving modulating a sirtuin activity and / or a sirtuin mRNA and / or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and / or SIRT mRNA and / or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and / or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide. The present invention further provides active agents that modulate sirtuin activity or expression; and compositions, including pharmaceutical compositions, comprising the active agents.

The present invention relates to sirtuin 6 activating peptides derived from highly conserved regions of human Sirtuin (SIRT) proteins, and to a cosmetic or pharmaceutical composition comprising at least one sirtuin 6 activating peptide in a physiologically acceptable medium. The invention further relates to the utilization of a cosmetic composition to prevent and / or repair Deoxyribonucleic acid (DNA) degradation, improve telomere maintenance and reduce cellular senescence. The invention also applies to a cosmetic treatment process intended to prevent and / or treat the cutaneous signs of aging and photo aging.

The invention encompasses compositions and methods for effectively treating and / or preventing diabetes and / or obesity. This is accomplished by totally addressing the multiple mechanisms that lead to such conditions. The invention includes compositions comprising a combination of agents that effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that lead to diabetes and obesity. The inventive compositions used for administration to human and other mammalian subjects comprise (1) at least one agent capable of modulating expression and / or activity of one or more of peroxisome activated protein receptor gamma (PPAR-γ), CAAT / enhancer binding protein-α (C / EBPα) and Sterol Regulatory Element-Binding Protein (SREBP-1); (2) at least one agent capable of activating Wnt / β-catenin pathway; (3) at least one agent capable of activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway; (4) at least one agent that inhibits the activity of pro-oxidants including reactive nitrogen species and reactive oxygen species (ROS); (5) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2); (6) at least one agent capable of enhancing glucose transporter (GLUT4) and / or inhibiting glucose transporter GLUT2; (7) at least one agent that induces the expression of and / or activates adiponectin and (8) at least one agent that induces the expression of and / or activates sirtuin (SIRT1). The active agents for use herein are natural materials such as phytonutrients, vitamins and minerals. Compositions with combinations of such natural agents have the ability to prevent, reduce or treat diabetes and obesity by (a) clearing glucose and fatty acids from blood, (b) reducing the number of adipose cells and fat storage, (c) interfering with fat, glucose, and cholesterol biosynthesis, and (d) promoting fat and glucose oxidation.Since the present compositions are aimed toward normalizing metabolism and energy expenditure and managing oxidative stress and inflammation, they are also beneficial in relation to physical activity, in particular performance, endurance, fatigue and recovery during intensive and continuous exercise / exertion.

The described invention provides methods and compositions for enhancing the enzymatic activity of Sirtuin family members by using Leptin, Leptin analogs, Leptin derivatives, or Leptin agonists. The described invention further provides compositions and methods for delaying senescence or cell death in neurons using the compositions.

The present invention provides treatment methods involving modulating a sirtuin activity and / or a sirtuin mRNA and / or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and / or SIRT mRNA and / or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and / or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide. The present invention further provides active agents that modulate sirtuin activity or expression; and compositions, including pharmaceutical compositions, comprising the active agents.

The present invention relates to the use of SIRT7 (sirtuin 7) as a marker for diagnosis of liver cancer. More specifically, the invention relates to a liver cancer diagnostic marker comprising SIRT7 gene, a liver cancer diagnostic composition, kit and microarray comprising the same, and a method of diagnosing liver cancer using the same. The invention also relates to a method for screening a substance capable of preventing or treating liver cancer by inhibiting the expression of SIRT7 gene or protein, and to a composition for preventing or treating liver cancer, which comprises the substance. The expression level of SIRT7 gene is higher in liver cancer tissue or cells than in non-liver cancer tissue or cells. Thus, when SIRT7 gene is used as a cancer diagnostic marker, cancer can be early diagnosed and predicted in a rapid and accurate manner, and it can be used as a target for development of an agent for preventing or treating cancer. Moreover, the invention is based on the finding that the expression of SIRT7 gene is indicative of the development and proliferation of cancer cells, and cell cycle transition, and thus the invention relates to the use of SIRT7 gene as a cancer diagnostic marker and to the anticancer use of inhibition of SIRT7 expression. In addition, the invention is based on the relationship between the SIRT7 expression and a specific miRNA, and thus relates to the use of the specific miRNA to regulate the cell cycle and inhibit tumor growth.

The present invention provides a general method for identify agents that modulate the activity of histone modifying enzymes, such as an acetylase, deacetylase, methyltransferase, demethylase, kinase, etc. The assay the of invention employs reconstituted, immobilized nucleosomes and fluorescence-based assays, such as fluorescence-based immunoassays, scintillation proximity assays, or FRET assays to determine whether the agent modulates the activity of the histone modifying enzymes.