Transcriptomic profiling of mouse aging soleus muscles and drug interventions

Here, we performed bulk RNA sequencing on soleus muscles of both male and female mice at four different life stages (6, 12, 20, and 28 months). We showed that aging soleus muscle mice follows and shift on gene expression pattern during aging. Network analysis showed that modules enriched in mitochondria showed a down-then-up trend during aging, resembles the expression pattern of longevity-associated modules in C.elegans. We also associated expression of conserved module with frailty and found that the expression of the mitochondria/ribosome module is positively associated with frailty at 28 months in male mice. In addition, we treated mice with four different compounds from 20 months to 28 months, recorded their frailty change over time and performed RNA-seq on their soleus muscles. We found that aKG treatment in male mice significantly reduced frailty index and exhibted an decrease in expression of mitochondria/ribosome modules. Together, we represent a large transcriptomic cohort of aging and drug interventions on mouse soleus muscles. Our study showed the sex-specific beneficial effects on compounds that identified conserved co-expression modules during aging that are associated with longevity.