Project description:Identification of genes altered by aging in the human liver We identified genes that were differentially expressed in males only, females only, or in all individuals between the young and old using microarray.
Project description:We explored how aging impacts transcriptional dynamics using single-cell RNA-sequencing to profile hundreds of CD4+ T cells from young and old mice from two divergent species. In young animals, immunological challenge drives a conserved transcriptomic switch from highly variable to tightly regulated gene expression, characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging significantly perturbed the activation of this core program, and increased expression heterogeneity across the population of cells in both species.
Project description:Aging is a major risk factor for the development of many diseases, and liver as the most important metabolic organ is significantly affected by aging. Earlier studies have shown that liver weight tends to increase and decrease with age in rodents and human, respectively. Intriguingly, the pig has a genomic structure, physiological and biochemical features similar to those of humans, and has been found to be a valuable model for studying human diseases. Moreover, the molecular mechanisms of large mammal’s liver aging in a comprehensive transcriptional level has been poorly understood. Therefore, the pig can be an ideal model animal to clearly and fully understand the molecular mechanism of human liver aging. We have identified many age-related genes in the porcine liver, GO annotation showed that up-regulated genes were mainly related to immune response, and the down-regulated genes were mainly involved in metabolism. Moreover, some lncRNAs and their target genes were also found differentially expressed during liver aging. In addition, we assessed the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks during liver aging.
Project description:This project aims to identify DNA methylation changes that occur during liver aging and regeneration using a whole-genome single nucleotide resolution approach and determine the genes and pathways associated with the differentially methylated genomic regions (DMRs) that are co-regulated by aging and regeneration
Project description:Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here we examined the effects of Klotho on MO3.13, a human oligodendroglioma cell line in order to determine the potential role of Klotho as a tumor suppressor. We show that exogenous Klotho affects the ERK and Akt signaling pathways and decreases the proliferative abilities of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80% of the differentially expressed genes being downregulated. Using gene set enrichment analysis we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain malignancies. 6 Samples
Project description:Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. To determine how our dietary intervention-based transcriptomic approach for predicting aging-regulatory genes compares to more traditional approach of using age-dependent transcriptional changes, we examined the hepatic gene expression changes in LF-fed mice during aging at 4, 8, 13 and 21 months. Male C57BL/6J mice at 4 weeks of age were purchased from Shanghai Animal Co, Ltd. Mice were maintained under a 12-hour dark/light cycle (lights on at 6:30 am) at a temperature of 22 ± 3 °C in accredited animal facilities. Prior to the start of experiment, mice were maintained on a low-fat diet (Research Diets Inc., New Brunswick, NJ) for one week. Liver RNAs extracted from six male C57BL/6J mice of the same age were pooled at each age point to obtain an average microarray profile at 4, 8, 13 and 21 months.