The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan. Overall design: RNAsequencing expression profiles of livers and triceps surae hindlimb muscle from 25 week-old Ins1-/-;Ins2+/- and Ins1-/-;Ins2+/+ littermate control mice on one of two different diets (Diet A and B)
Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.
Sex, Age, Specimen part, Cell line, Subject
View Samples14-3-3 proteins facilitate cytoplasmic-nuclear shuttling of transcription factors.Adipocyte differentiation requires the function of critical transcription factors to drive the development of a mature adipocyte. The aim of the study was to investigate if 14-3-3? is required for the adipogenic transcriptional program. Overall design: Examination of the transcriptome in siCon- and si14-3-3?-transfected 3T3-L1 cells undergoing differentiation at t=0, 24, and 48 hours.
14-3-3ζ coordinates adipogenesis of visceral fat.
No sample metadata fields
View SamplesDue to inherent differences in adipcoyte size between wildtype and knockout animals, we sought to examine if the decrease in adipocyte size was due to differences in the transcriptome and more specifcially, adipogenic genes. Overall design: Examination of the transcriptome in wildtype (WT) and knockout (KO) gonadal white adipose tissue from adult mice
14-3-3ζ coordinates adipogenesis of visceral fat.
No sample metadata fields
View SamplesWe define the effects of reduced insulin production in beta-cells from tamoxifen-treated Ins1-/-:Ins2f/f:Pdx1CreERT:mTmG mice studied at a time point when insulin production was reduced by ~50%. Overall design: Examination of the transcriptome of adult pancreatic islets from mice with acute Ins2 gene knockout out on an Ins1 null background
Reduced Insulin Production Relieves Endoplasmic Reticulum Stress and Induces β Cell Proliferation.
Specimen part, Treatment, Subject
View SamplesActivation of telomerase often endows cancer cells, but rarely normal somatic cells, with immortality. Especially, fetal lung fibroblasts are known to be hardly immortalized by TERT overexpression. We here established an immortal non-transformed lung fibroblast cell line only by TERT transfection, as well as an immortal transformed cell line by transfection of TERT and SV40 early antigens. Comparing the expression profiles of these cell lines with those of mortal cell strains with elongated lifespan after TERT transfection, 51 genes, including 19 upregulated and 32 downregulated, were explored to be the candidates responsible for regulation of cellular proliferation of lung fibroblasts. These included the genes previously reported to be involved in cellular proliferation, transformation, or self-renewal capacity, and those highly expressed in lung tissues obtained from patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis. This set of lung fibrobrast cell lines/strains of identical genetic background with different proliferative capacity, mortal and immortal non-transformed fibroblasts may become useful model cells for research on lung fibroblast growth regulation and the candidate genes explored in this study may provide promising biomarkers or molecular targets of pulmonary fibrosis.
Exploration of the genes responsible for unlimited proliferation of immortalized lung fibroblasts.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.
No sample metadata fields
View SamplesUtilizing C. elegans as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease. We characterized genome-wide expression profiles of hypomorhpic C. elegans mutants in nuclear-encoded subunits of respiratory chain complexes I, II and III.
Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.
No sample metadata fields
View SamplesUtilizing C. elegans as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease. We characterized genome-wide expression profiles of hypomorphic C. ele
Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans.
No sample metadata fields
View SamplesScreening for genes regulated by Etv2 within Flk-1+/PDGFRa+ ES derived mesoderm.Microarray analysis performed to screen for the candidate genes regulated by Etv2. TT2 ES cells differentiated on OP9 feeder cells were sorted using Flk-1 and PDGFRa antibodies.Gene expressions from these two populations were compared.
Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm.
Cell line
View SamplesScreening for genes up in Etv2+ cells within Flk-1+ ES derived mesoderm
Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm.
Cell line
View Samples