Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2019-09, Vol.317 (3), p.R397-R406
• Main Authors: Mumford, Petey W, Romero, Matthew A, Osburn, Shelby C, Roberson, Paul A, Vann, Christopher G, Mobley, Christopher B, Brown, Michael D, Kavazis, Andreas N, Young, Kaelin C, Roberts, Michael D
• Format: Article
• Language: English
• Subjects: Accessibility; Acetylation; Aging - physiology; Animals; Biomarkers; Citrate (si)-Synthase - genetics; Citrate (si)-Synthase - metabolism; Collagen - genetics; Collagen - metabolism; Deoxyribonucleic acid; DNA; DNA methylation; DNA methyltransferase; DNA sequencing; Gastrocnemius muscle; Gene Expression Regulation - physiology; Genomes; HDAC2 protein; Histone deacetylase; Histones; Long interspersed nucleotide elements; Long Interspersed Nucleotide Elements - physiology; Male; Markers; mRNA; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - anatomy & histology; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Primers; Rats; Rats, Inbred F344; Replication; Rodents; Skeletal muscle; Triglycerides - blood; Up-Regulation
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00110.2019

Long interspersed element-1 (LINE-1) is a retrotransposon capable of replicating and inserting LINE-1 copies into the genome. Others have reported skeletal muscle LINE-1 markers are higher in older versus younger mice, but data are lacking in other species. Herein, gastrocnemius muscle from male Fischer 344 rats that were 3, 12, and 24 mo old ( = 9 per group) were analyzed for LINE-1 mRNA, DNA, promoter methylation and DNA accessibility. qPCR primers were designed for active (L1.3) and inactive (L1.Tot) LINE-1 elements as well as part of the ORF1 sequence. L1.3, L1.Tot, and ORF1 mRNAs were higher ( < 0.05) in 12/24 versus 3-mo-old rats. L1.3 DNA was higher in the 24-mo-old rats versus other groups, and ORF1 DNA was greater in 12/24 versus 3-mo-old rats. ORF1 protein was higher in 12/24 versus 3-mo-old rats. RNA-sequencing indicated mRNAs related to DNA methylation ( ) and histone acetylation ( ) were lower in 24 versus 3-mo-old rats. L1.3 DNA accessibility was higher in 24-mo-old versus 3-mo-old rats. No age-related differences in nuclear histone deacetylase (HDAC) activity existed, although nuclear DNA methyltransferase (DNMT) activity was lower in 12/24 versus 3-mo-old rats ( < 0.05). In summary, markers of skeletal muscle LINE-1 activity increase across the age spectrum of rats, and this may be related to deficits in DNMT activity and/or increased LINE-1 DNA accessibility.