Project description:Multi-omics analysis is relatively rare in aging research and has not been used for aging liver study by now. Here, we performed metabolome, proteome and acetylome with livers of 2-month-old and 18-month-old mice.
Project description:Aging is associated with extensive transcriptional and cellular changes in the liver, including the emergence of metabolically dysfunctional and stress-responsive hepatocyte states. Adenosine kinase (ADK) is a key regulator of intracellular and extracellular adenosine homeostasis; however, its contribution to age-associated liver remodeling remains incompletely understood. To characterize liver aging at single-nucleus resolution and investigate the role of hepatocyte ADK, we performed single-nucleus RNA sequencing of liver tissues from 3-month-old wild-type mice, 18-month-old wild-type mice, and 18-month-old mice carrying hepatocyte-specific ADK wild-type or heterozygous alleles. Comparative transcriptomic analyses were used to identify age-associated changes in hepatic cell populations, characterize distinct hepatocyte states, and determine how partial reduction of hepatocyte ADK influences aging-related transcriptional programs. This dataset provides a resource for investigating cellular heterogeneity, hepatocyte aging, and ADK-dependent regulation in the aged mouse liver.
Project description:Caspase-2 function in liver homeostasis is influenced by its important role in mitotic catastrophe to prevent survival and accumulation of aneuploid and polyploid cells. While loss of caspase-2 promotes hepatocyte polyploidy, it is unclear how this influences liver homeostasis with ageing. To address this, this project examined age-related liver proteomic changes, in caspase-2 deficient mice (knockout and catalytic cytsteine mutant- C320S), comparing protein abundance in young (3-month-old) and ageing (12 and 18-month-old) mice. We describe changes in several cell-cycle related and inflammation-related proteins that are associated with early hepatocyte hyperpolyploidy in young caspase-2- deficient mice, as well as increased liver disease in ageing caspase-2 deficient mice. These findings demonstrate that caspase-2 catalytic activity is critical for age-related liver homeostasis by preventing pathogenic hyperpolyploidy, tissue inflammation, tissue damage and survival of pre-neoplastic cells.
Project description:Lean nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a distinct clinical phenotype with limited evidence for effective non-pharmacological interventions and unclear mechanistic pathways. Aerobic exercise is recommended for NAFLD management; however, its effects and the gut microbiota–associated mechanisms in lean NAFLD remain incompletely understood. This dataset was generated from a randomized controlled trial (ClinicalTrials.gov identifier: NCT04882644). Participants assigned to the aerobic exercise intervention group provided fecal samples at baseline and after the 3-month intervention. A total of 33 paired fecal samples were included in this dataset. Gut microbiota profiles were generated using shotgun metagenomic sequencing. The dataset includes processed and de-identified species-level relative abundance tables derived from fecal samples collected before and after the intervention. These data were used to characterize exercise-induced alterations in gut microbial composition and interindividual variability in microbiota responses to aerobic exercise in lean NAFLD. The data support integrative analyses with clinical phenotypes and circulating metabolomic profiles to explore gut microbiota–associated mechanisms underlying the metabolic benefits of aerobic exercise.
Project description:The aim of this study was to test the hypothesis that replenishing the microbiota with a fecal microbiota transplant (FMT) can rescue a host from an advanced stage of sepsis. We developed a clinically-relevant mouse model of lethal polymicrobial gut-derived sepsis in mice using a 4-member pathogen community (Candida albicans, Klebsiella oxytoca, Serratia marcescens, Enterococcus faecalis) isolated from a critically ill patient. In order to mimic pre-operative surgical patient condition mice were exposed to food restriction and antibiotics. Approximately 18 hours prior to surgery food was removed from the cages and the mice were allowed only tap water. Each mouse received an intramuscular Cefoxitin injection 30 minutes prior to the incision at a concentration of 25 mg/kg into the left thigh. Mice were then subjected to a midline laparotomy, 30% hepatectomy of the left lateral lobe of the liver and a direct cecal inoculation of 200 µL of the four pathogen community. On postoperative day one, the mice were administered rectal enema. Mice were given either 1 ml of fecal microbiota transplant (FMT) or an autoclaved control (AC). This was again repeated on postoperative day two. Mice were then followed for mortality. Chow was restored to the cages on postoperative day two, approximately 45 hours after the operation. The injection of fecal microbiota transplant by enema significantly protected mice survival, reversed the composition of gut microflora and down-regulated the host inflammatory response. The cecum, left lobe of the liver, and spleen were isolated from mice for microarray processing with three or more replicates for six expermental conditions: non-treated control, SAHC POD1, SAHC.AC POD2, SAHC.FMT POD2, SAHC.AC POD7, SAHC.FMT POD7
Project description:Lean nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a distinct clinical phenotype with limited evidence for effective non-pharmacological interventions and unclear mechanistic pathways. Aerobic exercise is recommended for NAFLD management, yet its effects and underlying gut microbiota–mediated mechanisms in lean NAFLD remain insufficiently characterized. This study is based on a randomized controlled trial (ClinicalTrials.gov identifier: NCT04882644) in which 100 adults with lean NAFLD were randomly assigned to a 3-month aerobic exercise intervention or usual care. 63 paired fecal samples were collected at baseline and after intervention. Gut microbiota profiles were generated using 16S rRNA gene sequencing. The dataset includes processed taxonomic abundance tables derived from fecal samples collected before and after the intervention. These data were used to characterize exercise-induced alterations in gut microbial diversity, composition, and functional potential, and to explore interindividual heterogeneity in microbiota responses to aerobic exercise in lean NAFLD. The microbiome data deposited in this series support integrative analyses with clinical phenotypes and circulating metabolomic profiles, aiming to elucidate gut microbiota–associated mechanisms underlying the metabolic benefits of aerobic exercise in lean NAFLD.
Project description:We report age related DNA methylation changes in mice in Small intestine, Colon, Heart, Lungs, Liver, Spleen, Kidney and Whole hlood across 3 different aging timepoints (4 month, 12 month, 24 month). For small intestine and colon there are 4 aging time points ( 4 month, 12 month, 18 month and 24 month)
Project description:The aim of this study was to test the hypothesis that replenishing the microbiota with a fecal microbiota transplant (FMT) can rescue a host from an advanced stage of sepsis. We developed a clinically-relevant mouse model of lethal polymicrobial gut-derived sepsis in mice using a 4-member pathogen community (Candida albicans, Klebsiella oxytoca, Serratia marcescens, Enterococcus faecalis) isolated from a critically ill patient. In order to mimic pre-operative surgical patient condition mice were exposed to food restriction and antibiotics. Approximately 18 hours prior to surgery food was removed from the cages and the mice were allowed only tap water. Each mouse received an intramuscular Cefoxitin injection 30 minutes prior to the incision at a concentration of 25 mg/kg into the left thigh. Mice were then subjected to a midline laparotomy, 30% hepatectomy of the left lateral lobe of the liver and a direct cecal inoculation of 200 µL of the four pathogen community. On postoperative day one, the mice were administered rectal enema. Mice were given either 1 ml of fecal microbiota transplant (FMT) or an autoclaved control (AC). This was again repeated on postoperative day two. Mice were then followed for mortality. Chow was restored to the cages on postoperative day two, approximately 45 hours after the operation. The injection of fecal microbiota transplant by enema significantly protected mice survival, reversed the composition of gut microflora and down-regulated the host inflammatory response.
Project description:RNA from three hepatocellular carcinomas from 24-month-old SRSF3HKO mice compared to RNA from non-tumorous liver from 24-month-old SRSF3HKO mice for changes in exon utilization and gene expression.