RNA-sequencing reveals a gene expression signature in skeletal muscle of a mouse model of age-associated post-operative functional decline

This study aimed to characterize the effects of laparotomy on post-operative physical function and skeletal muscle gene expression in C57BL/6N mice at 3, 20 and 24 months of age to investigate late-life vulnerability and resiliency to acute surgical stress. Pre- and post-operative physical functioning were assessed by forelimb grip strength and motor coordination on the accelerating rotarod. RNA sequencing of soleus muscles collected on post-operative day 5 (POD 5) showed that laparotomy induced age-associated differential gene expression and canonical pathway activation with the greatest effects in the youngest mice. The 24-month-old mice were stratified into low functioning (LF) and high functioning (HF) groups based on their baseline motor performance on the accelerating rotarod. RNA-sequencing showed 224 and 228 differentially expressed genes (DEGs) for HF and LF, respectively, compared to their respective controls. Only 21 DEGs were observed in both groups. We conclude that pre-operative performance on the accelerating rotarod correlates with differences in skeletal muscle gene expression, which may contribute to the differences in functional outcomes post-operatively in HF and LF mice. These findings demonstrate a mouse model of laparotomy which recapitulated some features of post-operative skeletal muscle decline in older adults following surgery, and identified age-associated, laparotomy-induced molecular signatures in skeletal muscles. 24 soleus muscle samples from C57BL/6N male mice were analyzed by RNA-sequencing. Muscles were collected from the laparotomy groups and age matched control groups 5 days post laparotomy surgery. 6 samples (3 replicates for control and 3 replicates for laparotomy) were analyzed per age group for the 3-month-old and 20-month-old groups. Two groups of 24-month-old mice were analyzed. They were designated as 24-month-old low functioning (LF) and 24-month-old high functioning (HF) groups based on the animal’s performance on the accelerating rotarod. Both 24-month-old groups contained 6 samples, 3 replicates for control and 3 replicates for laparotomy. For all groups the expression levels for the laparotomy group was compared to control group.