Aging,an inevitable process of life development,reflects the functional recession of the entire organism.According to the "Shennong Materia Medica",Ganoderma lucidum is categorized as the "medicinal and food homology" and has the effect of strengthening body resistance and prolonging life.Ganoderma lucidum is composed of various active ingredients,including ganoderma lucidum polysaccharides,triterpenoids,nucleosides,and proteins.Manganese,iron,zinc,selenium and other microelements have also been confirmed to be part of it.Significant immunoregulation,antineoplastic activity and hypoglycemic effect form the pharmacological feature of Ganoderma lucidum.However,the effectiveness of Ganoderma lucidum in anti-aging has been controversial.Therefore,this research establishes an intervention model in natural aging C57BL/6J male mice for the purpose to systematically study the anti-aging effect and mechanism of Ganoderma lucidum through the aspects of behavior,methylation omics,intestinal flora,and transcriptomics.The main results are shown below:(1)Ganoderma lucidum intervention could improve the aging phenotype of mice,including hunchback phenomenon,hair density and brightness.Long-term interventions significantly reduced the weight of mice.(2)The methylation age of mice was estimated using three methylation sites:Prima1,Hsf4,and Kcns1.The results suggested that Ganoderma lucidum intervention was connected with the methylation age of mice.After 20 weeks of intervention,the methylation age of mice in intervention group was slightly lower than the control group.(3)16S r DNA sequencing was applied to explore the effect of Ganoderma lucidum intervention on intestinal flora.Feeding naturally senescent mice with Ganoderma lucidum can significantly change the β diversity,affect the abundance and diversity of intestinal strains,and decrease the flora correlation.The abundance of probiotics increased,and the abundance of conditioned pathogenic bacteria educed.(4)The effects of Ganoderma lucidum intervention on gene expression was measured by transcriptome sequencing.The results showed that senescent genes Angpt1 and Atp6v1 h associated with heart function were significantly downregulated.(5)Behavioral experiments show that Ganoderma lucidum intervention has no significant influence on the motor ability,autonomous behavior and inquiry behavior of mice.In summary,this study uses methylation sequencing,16 S r DNA sequencing,transcriptome sequencing,and behavioral experiments to evaluate the effects of long-term Ganoderma lucidum intervention on naturally aging mice from multiple aspects.The results imply that long-term Ganoderma lucidum intervention affect the aging process of mice by altering the intestinal flora composition and abundance,and affecting cardiac-inflammation-associated gene expression. |