Project description:BackgroundAging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.ObjectiveTo explore the underlying mechanism of how aging aggravates AS advancement.MethodsA young (five-week-old, YM) and aged group (32-week-old, OM) male apoE-/- mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS.ResultsApoE-/- mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE-/- mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal flora composition among the four groups, and harmful bacteria such as Lachnospiraceae_FCS020, Ruminococcaceae_UCG-009, Acetatifactor, Lachnoclostridium and Lactobacillus_gasseri were significantly increased in the aged apoE-/- mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2α, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice.ConclusionsAging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.
Project description:The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorithm, we identified a set of key transcription factors (Egr1, Irf1, FosB) that drives molecular and functional differences between old and young states. Overall, by dissecting the molecular signature of aged ISCs, our study identified transcription factors that enhance the regenerative capacity of ISCs.
Project description:The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorithm, we identified a set of key transcription factors (Egr1, Irf1, FosB) that drives molecular and functional differences between old and young states. Overall, by dissecting the molecular signature of aged ISCs, our study identified transcription factors that enhance the regenerative capacity of ISCs.
Project description:The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorithm, we identified a set of key transcription factors (Egr1, Irf1, FosB) that drives molecular and functional differences between old and young states. Overall, by dissecting the molecular signature of aged ISCs, our study identified transcription factors that enhance the regenerative capacity of ISCs.
Project description:To explore the effects of gut microbiota of young (8 weeks) or old mice (18~20 months) on stroke, feces of young (Y1-Y9) and old mice (O6-O16) were collected and analyzed by 16s rRNA sequencing. Then stroke model was established on young mouse receive feces from old mouse (DOT1-15) and young mouse receive feces from young mouse (DYT1-15). 16s rRNA sequencing were also performed for those young mice received feces from young and old mice.
Project description:Background: Bowel preparation is necessary for successful colonoscopy, while it can seriously affect intestinal microbial composition and damage the intestinal mucosal barriers in humans. Methods: To figure out whether probiotics can sustain intestinal homeostasis and guard people's health, the probiotic drug of Bifidobacterium Tetragenous viable Bacteria Tablets (P group, n = 16) or placebo (C group, n = 16) was used for volunteers receiving bowel preparation, and high-throughput sequencing method was applied to monitor their intestinal microbial changes. Results: The present results suggested that bowel preparation obviously reduced the intestinal microbial diversity, while taking probiotics significantly restored it to normal level. In addition, probiotics sharply reduced the abundance of pathogenic Proteobacteria, and obviously lowered the ratio of Firmicutes/Bacteroidetes compared with control group at phylum level (P < 0.05). And probiotics markedly decreased the abundance of pathogenic Acinetobacter and Streptococcus, while greatly enriched the relative abundance of beneficial bacteria Bacteroides, Roseburia, Faecalibacterium, and Parabacteroides at genus level (P < 0.05). Conclusion: Probiotic drugs, e.g., Bifidobacterium Tetragenous viable Bacteria Tablets, can be used to restore intestinal dysbacteriosis caused by bowel preparation, and reduce side effects during colonoscopy.
Project description:To examine underlying differences in gene expression between young and old MSCs and the effects of exposure of old MSCs to media conditioned by young MSCs on gene expression we performed RNA sequencing
Project description:Anabolic activities such as ribosome biogenesis and protein synthesis are linked to aging. Ribosomal RNA (rRNA) synthesis is the limiting step of ribosome biogenesis, thus dictating the number of ribosomes in cells and, consequently, the capacity for mRNA translation. Knockdown of the rRNA synthesis repressor, NCL-1, accelerated aging, whereas knocking down the transcription initiation factor C36E8.1 promoted longevity. This suggested that rRNA synthesis has a negative correlation with lifespan. To investigate the metabolic changes upon manipulation of rRNA synthesis the proteome of NCL-1 KD and C36E8.1 KD were analyzed at young, middle, and old age (AD2, AD6, AD12).