Integrative Multi-Omics Analysis Of The Anti-aging Effects Of Salidroside

Salidroside(SAL)is the main active component of the traditional Chinese medicine Rhodiola rosea.Previous studies showed that SAL possesses antiinflammatory,anti-cancer,anti-aging,and anti-neurodegenerative diseases properties.It has been found that salidroside can extend the lifespan of C.elegans and fish,but the mechanisms are largely unknown.This study is to examine SAL anti-aging effects using C57BL/6J mice based on multi-omics data.Twenty-four mice were randomly assigned into one of two groups: control or Salidroside(SAL).DNA methylation,RNASeq and 16 S rDNA were used to explore the effects of SAL on DNA aging clock,gene expression and gut microbiome,respectively.DNA methylation ages were calculated based on three methylation sites in Prima1,Hsf4 and Kcns1.We found no statistically significant difference in the DNA methylation age between treated and untreated mice.For gut microbiome,we examined the intestinal flora with 16 S rDNA sequencing.By analyzing the composition of the intestinal flora,we found that salidroside doesn’t change the intestinal flora strains but significantly alters their relative abundances(e.g.f＿Lactobacillaceae,g＿Parasutterella and o＿Bacteroidales).The correlation network analysis revealed a strong strain correlation of gut microbiota.To test SAL treatment on the age-related gene expression,we performed transcriptome analysis.Our results showed there is no significant difference in gene expression of the heart tissue.However,many genes in the brain tissue express significantly differently.Among them,three genes(Anxa1,Thbd,and Slc47a1)play a significant role in aging.We confirmed the altered gene expression via RT-qPCR and Western Blot.Our results suggest that SAL treatment may affect aging by inhibiting Anxa1,Thbd,and Slc47a1 expression.By analyzing gut microbiota and RNA-Seq data,we found methionine sulfoxide reductase A(Msra)expression is potentially regulated by the altered intestinal flora.Msra is an antioxidant and can reduce oxidized methionine to methionine.The Western Blot and RT-qPCR also confirmed a significant increase in Msra protein and m RNA levels in the SAL-treated group,suggesting SAL treatment may affect age-related gene expression through intestinal flora.In summary,we use multi-omics technologies to analyze the effects of SAL on aging in mice.We found that SAL treatment reduces the methylation age of mice at multiple time points but there is no statistical difference,suggesting additional analysis is needed.However,SAL may affect aging by changing the abundances of gut microbiotas and the many age-related gene expressions in the brain.