Project description:Aging causes a functional decline in tissues throughout the body that may be delayed by caloric restriction (CR). However, the cellular profiles and signatures of aging, as well as those ameliorated by CR, remain unclear. Here, we built comprehensive single-cell and single-nucleus transcriptomic atlases across various rat tissues undergoing aging and CR. CR attenuated aging-related changes in cell type composition, gene expression, and core transcriptional regulatory networks. Immune cells were increased during aging, and CR favorably reversed the aging-disturbed immune ecosystem. Computational prediction revealed that the abnormal cell-cell communication patterns observed during aging, including the excessive proinflammatory ligand-receptor interplay, were reversed by CR. Our work provides multi-tissue single-cell transcriptional landscapes associated with aging and CR in a mammal, enhances our understanding of the robustness of CR as a geroprotective intervention, and uncovers how metabolic intervention can act upon the immune system to modify the process of aging.
Project description:comparison of microRNA expression in the islets of 3- and 12-months old male Wistar rats Aging is a risk factor for a majority of metabolic diseases including type 2 diabetes. During aging pancreatic beta-cell function decreases leading to impaired insulin secretion and proliferation and to an increase in apoptosis. Impairment of pancreatic beta cell functions and survival has been linked to gene expression changes. The aim of our study was to obtain a global expression profile of microRNAs and mRNAs of pancreatic islets of 3 and 12 month old male Wistar rats in order to identify the changes occurring during aging.
Project description:Aging is associated with fundamental changes in pancreatic B-cell physiology; yet, the mechanisms that drive these age-related changes are poorly understood. We performed comprehensive proteomic profiling of pancreatic islets from adolescent and old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism not reflected at the transcript level. We show that these changes in protein abundance are associated with increased activity of the amplifying pathway of insulin secretion. The amplifying pathway stimulates insulin secretion through coupling factors produced during glucose metabolism. Nutrient tracing and targeted metabolomics demonstrate accelerated accumulation of glucose-derived metabolites and coupling factors in aged islets, indicating that age-related changes in glucose metabolism contribute to the improved response of B-cells to glucose with age. Together, our study provides the first in-depth characterization of changes in the islet proteome during aging and establishes metabolic rewiring as an important mechanism for age-associated changes in B-cell function.
Project description:There is mounting evidence indicating that piRNAs are also present in somatic cells where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta-cell activities. piRNA profiling of rat pancreatic islets was performed by microarray. We detected about 18’000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development.
Project description:Early postnatal overnutrition causes persistent dysregulation of endocrine pancreas function. We used genome-scale DNA methylation profiling in the suckling-period small litter (SL) mouse model to test whether this occurs via persistent epigenetic changes in pancreatic islets. Although SL islets showed DNA methylation changes directly after weaning and in adulthood, few of these were present at both ages, contrary to our hypothesis. Most interestingly, we discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging. Focusing on a subset of genes relevant to β cell function, we showed that these methylation differences are strongly correlated with expression. Together, our results provide the novel insight that DNA methylation changes that occur as islets age indicate an overall epigenetic drift toward the exocrine pancreas epigenome. These concerted shifts in the islet methylome could contribute to the age-associated decline in endocrine pancreas function. Pancreatic islets were isolated from P21/P180 SL or C mice. To ensure purity of islets, 3 rounds of manual picking were performed in each samples. Whole pancreas samples, ~98% of which is exocrine pancreas, were used as exocrine pancreas. There are 5 mice per group.