Abstract: The present disclosure provides methods of reducing protein misfolding and/or aggregation in a cell. The present disclosure provides methods of treating diseases and disorders associated with protein misfolding and/or aggregation.

Abstract: The disclosure features compositions and methods for treating a metabolic disorder, including diabetes, conditions associated with inhibition of insulin secretion, or for increasing longevity. In some embodiments, the methods comprise administering an anti-CGRP antagonist antibody.

Abstract: The disclosure provides methods and compositions useful for screening inhibitors of aggregation mediated proteotoxicity. The disclosure provides transgenic animals and cell useful for such screening. Also provided are compounds useful for inhibiting aggregation mediated proteotoxicity in a subject.

Abstract: Methods of modulating proteasome activity, increasing life span and neurogenesis are provided herein.

Abstract: The invention is directed to a method of treating a patient suffering from Alzheimer's disease comprising administering to said patient an agent that reduces the activity of the IGF-1 signaling pathway.

Abstract: The invention relates to the field of longevity enhancement. More particularly, the invention provides compositions and methods relating to CRTC modulation. In certain embodiments, the invention provides compositions and methods for enhancing longevity in an organism by inhibiting CRTC activity, such as, for example, inhibiting CRTC expression or cellular localization in the organism.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: The invention relates to the field of longevity enhancement. More particularly, the invention provides compositions and methods relating to modulation of mitochondrial function. In certain embodiments, the invention provides methods and related compositions for the enhancement of longevity in an animal, comprising inhibition of one or more electron transport chain components, such as cco-1 and homologs thereof, in a tissue-specific manner in the animal.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek gene to modulate both longevity and stress tolerance, are described.

Abstract: The disclosure provides methods and compositions useful for screening inhibitors of aggregation mediated proteotoxicity. The disclosure provides transgenic animals and cell useful for such screening. Also provided are compounds useful for inhibiting aggregation mediated proteotoxicity in a subject.

Abstract: The present invention relates to regulation of adult lifespan in eukaryotes. More particularly, the present invention is directed to methods of assaying for activators of the heat shock factor 1 (HSF-1) protein, which increases lifespan when overexpressed in an organism.

Abstract: Methods for identifying a cellular modulator of a biological disaggregation activity or a biological aggregation activity of an animal are provided. Methods for identifying a compound which modulates biological disaggregation activity or a biological aggregation activity in a biological sample are provided.

Abstract: The roles of the pha-4 and daf-16 genes in diet-restricted induced longevity are described and characterized. Pha-4 acts, e.g., in the absence of daf-16, to increase lifespan, e.g., in nematodes. Given the role that pha-4 and daf-16 play in the mediation of longevity, they represent targets for modulation of life span. Methods of increasing life span and delaying age onset diseases by modulation of pha-4 activity are disclosed, as are screening methods for identifying compounds that modulate pha-4 and/or daf-16 activity. In addition, recombinant animals expressing the pha-4 gene and not the daf-16 gene, and methods of using the pha-4 and/or daf-16 genes to modulate longevity and age-onset diseases are described.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek gene to modulate both longevity and stress tolerance, are described.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek genet to modulate both longevity and stress tolerance, are described.

Abstract: The present invention relates to regulation of lifespan in eukaryotes. More particularly, one aspect of the present invention is the identification of genes, gene products, and genes in pathways controlled by such genes and gene products, using RNAi and microarray analysis, that regulate lifespan (e.g., extend or truncate adult lifespan) in eukaryotes such as invertebrates (e.g., C. elegans), plants, and mammals, e.g., humans. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, antisense nucleic acids, and ribozymes, that regulate, e.g., enhance, adult lifespan via modulation of aging associated proteins; as well as to the use of expression profiles, promoters, reporter genes, markers, and compositions in diagnosis and therapy related to lifespan extension, life expectancy, and aging. The present invention also relates to gene therapy involving lifespan associated genes.

Abstract: The present invention relates to regulation of adult lifespan in eukaryotes. More particularly, the present invention is directed to methods of assaying for genes, gene products, and genes in pathways controlled by such genes and gene products, using RNAi and microarray analysis, that regulate lifespan (e.g., extend or truncate adult lifespan) in eukaryotes such as invertebrates (e.g., C. elegans), plants, and mammals, e.g., humans. For example, the present invention is directed to genes encoding components of the mitochondrial respiratory chain and genes encoding glycolysis enzymes, which are involved in lifespan regulation, and genes and gene products in pathways controlled by such genes.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek genet to modulate both longevity and stress tolerance, are described.