Tracking gene expression changes following aging of C. elegans
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ABSTRACT: Track down the differential gene expressions between young and aged C. elegans to build a aging metabolism map Track down the differential gene expressions between young and aged C. elegans to build a aging metabolism map
Project description:We investigated how aging impacts the ILC2 population in the brain. Through RNA-sequencing of 2-week culture of sorted brain ILC2 from young and aged mice,we identified differential gene expressions regarding cellular exhaustion and self-renewal between young and aged brain ILC2.
Project description:To examine gene expression changes duging aging in polyploid and diploid hepatocytes, diploid and polyploid hepatocytes were sorted from young and aged multi-reporter mice and their gene expressions were analyzed by high-throughput RNA sequence.
Project description:Low complexity “prion-like” domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components including stress granule proteins become highly insoluble with age in C. elegans and that reduced insulin/IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress granule-related RBP aggregates are associated with reduced fitness. We show that HSF-1 is a main regulator of stress granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress granule-related RBPs partly by reducing the build-up of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.
Project description:The transcriptomic changes of young and aged T cells are still unknown. Our previous study successfully tracked aged T cells generated from one wave of developing thymocytes of young age by a lineage-specific and inducible Cre-controlled reporter (TCRδCreERR26ZsGreen mouse strain). We used this transgenic mice and RNA-Seq to study the immunosenescence of naïve and memory T cell populations. A large number of genes involved in cellular and molecular functions, protein activity, cell cycle, cell adhesion, and immune functions were identified as having altered expression during aging. Our work revealed aged CD8 memory T cells with increased T cell activation and immunity genes, yet high expression of immunosuppressive checkpoints and resistance to cell death, implying aberrant T cell immunity in old mice. These feature genes identified in the current study serve as new therapeutic targets for correcting age-related defects.
Project description:Progenitor cells play fundamental roles in preserving optimal organismal functions under normal, aging, and disease conditions. However, progenitor cells are incompletely characterized, especially in the brain, partly because conventional methods are restricted by inadequate throughput and resolution for deciphering cell-type-specific proliferation and differentiation dynamics in vivo. Here, we developed TrackerSci, a new technique that combines in vivo labeling of newborn cells with single-cell combinatorial indexing to profile the single-cell chromatin landscape and transcriptome of rare progenitor cells and track cellular differentiation trajectories in vivo. We applied TrackerSci to analyze the epigenetic and gene expression dynamics of newborn cells across entire mouse brains spanning three age stages and in a mouse model of Alzheimer's disease. Leveraging the dataset, we identified diverse progenitor cell types less-characterized in conventional single cell analysis, and recovered their unique epigenetic signatures. We further quantified the cell-type-specific proliferation and differentiation potentials of progenitor cells, and identified the molecular programs underlying their aging-associated changes (e.g., reduced neurogenesis/oligodendrogenesis). Finally, we expanded our analysis to study progenitor cells in the aged human brain through profiling ~800,000 single-cell transcriptomes across five anatomical regions from six aged human brains. We further explored the transcriptome signatures that are shared or divergent between human and mouse oligodendrogenesis, as well as the region-specific down-regulation of oligodendrogenesis in the human cerebellum. Together, the data provide an in-depth view of rare progenitor cells in mammalian brains. We anticipate TrackerSci will be broadly applicable to characterize cell-type-specific temporal dynamics in diverse systems.
Project description:We report here that in C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis, and, accordingly, extends fecundity and reproductive span.
Project description:We performed label-free proteomics in C. elegans to define and quantify changes in the ubiquitinated (Ub)-proteome during the aging process. More specifically, we compared wild-type worms at the first day of adulthood with young (day 5), mid-age (day 10) and aged adults (day 15). Moreover, we assessed protein levels of age-matched long-lived genetic models of dietary restriction (eat-2(ad1116)) and reduced insulin/IGF-1 signaling (daf-2(e1370)).
Project description:This program aims at identifying a muscle gene signature associated with aging in rat sarcopenia model The profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in the muscle of aged rats compared to the young controls.
Project description:To study the protective effects of preoperative fasting against renal ischemia-reperfusion injury, young-lean as well as aged overweight mice were subjected to three days of fasting or ad libitum food consumption, and gene expressions in kidneys of male mice were analyzed 19 samples (5 young control, 4 young fasted, 5 aged control, 5 aged fasted), each from individual mice