Effects of long-term voluntary exercise and aging in rats on markers of Long Interspersed Nuclear Element-1 (L1) activity in skeletal muscle, liver, and brain tissue

Abstract

Long Interspersed Nuclear Element-1 (LINE-1 or L1) is the only active mammalian TE. L1 is an autonomous retrotransposon that is able to “copy and paste” itself, increasing its presence as it does so and leading to genomic instability. L1 has been implicated in multiple diseases and the aging process. Our laboratory has shown L1 expression and regulation can be favorably altered through acute exercise, highlighting another aspect of the importance of exercise in maintaining health and cell integrity. We sought to determine the effects of chronic, voluntary wheel running on L1 expression and regulation, as well as markers of the cGAS-STING inflammatory pathway. Female Lewis rats (n=34) were separated into one of three groups. A group analyzed at 6 months old to serve as a young comparator group (CTL, n=10). From there, two groups were aged out to 15 months old. One group had access to a running wheel for voluntary wheel running from 6 months to 15 months of age (EX, n=12), while the other group did not and served as a sedentary control from 6 months to 15 months of age (SED, n=12). Plantaris, soleus, liver, and hippocampus tissues were harvested, and RNA, DNA, and protein were isolated for analysis. Methylation of the L1 promoter was significantly higher in SED and EX compared to CTL for both L1-3 and L1-Tot (p=0.021 and p=0.028, respectively) in the soleus and hippocampus tissues. ORF1p expression was higher in older SED and EX rats compared to CTL for every tissue. There were no differences between groups in protein expression for the cGAS-STING pathway markers. Our results suggest there is an increased ORF1p protein expression across tissues with aging that is not mitigated by voluntary wheel running. Additionally, while previous data imply that L1 methylation changes play may a role in acute exercise for L1 RNA expression, this does not seem to occur during extended periods of voluntary wheel running.