Abstract: Provided herein are sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract: Provided herein are Sirt1 polymorphic variants having a substitution at amino acid residue 107 or nucleotide 373. In certain embodiments, the Sirt1 polypeptide variants have a L107P substitution and the nucleic acid variants have a T373C substitution. Genetic and/or biochemical testing may be performed to identify whether a patient carries one of the disclosed polymorphic variants. Based on the polymorphic variant the patient carries, a medical practitioner may administer an appropriate therapy, such as a sirtuin activator.

Abstract: In general, the invention features methods and uses for transposon-mediated gene targeting which greatly enhance the insertion and detection of desired genes in genomic exons by homologous recombination. The invention also features transgenic non-human mammals, and eukaryotic cells, wherein a gene encoding 7B2 protein is modified, as well as nucleic acid vectors capable of undergoing homologous recombination with an endogenous 7B2 gene in a cell. The invention also features transgenic non-human mammals as models of endocrine disorders, as well as methods for diagnosing and treating patients with endocrine disorders.

Abstract: In general, the invention features methods and uses for transposon-mediated gene targeting which greatly enhance the insertion and detection of desired genes in genomic exons by homologous recombination. The invention also features transgenic non-human mammals, and eukaryotic cells, wherein a gene encoding 7B2 protein is modified, as well as nucleic acid vectors capable of undergoing homologous recombination with an endogenous 7B2 gene in a cell. The invention also features transgenic non-human mammals as models of endocrine disorders, as well as methods for diagnosing and treating patients with endocrine disorders.

Abstract: In general, the invention features methods and uses for transposon-mediated gene targeting which greatly enhance the insertion and detection of desired genes in genomic exons by homologous recombination. The invention also features transgenic non-human mammals, and eukaryotic cells, wherein a gene encoding 7B2 protein is modified, as well as nucleic acid vectors capable of undergoing homologous recombination with an endogenous 7B2 gene in a cell. The invention also features transgenic non-human mammals as models of endocrine disorders, as well as methods for diagnosing and treating patients with endocrine disorders.

Abstract: The present invention provides methods which greatly facilitate the rapidity in which cells and transgenic animals with targeted genes may be generated. The invention hastens the investigation of cells and transgenic animals bearing lowered expression of the targeted gene product, a truncated targeted gene product, a fusion protein of the targeted gene and exogenous DNA, or the expression of a different gene from the locus of the targeted gene whose product has reduced expression levels. Also disclosed is a transgenic animal having Cushing's disease. Also disclosed are diagnostic methods for detecting patients with endocrine disorders, and methods for treating or alleviating the symptoms of endocrine disorders.