Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats
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2019-09-01
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<jats:p> 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 ( n = 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 ( P < 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 ( Tet1) and histone acetylation ( Hdac2) 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 ( P < 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. </jats:p>
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Mumford, Petey W, Matthew A Romero, Shelby C Osburn, Paul A Roberson, Christopher G Vann, Christopher B Mobley, Michael D Brown, Andreas N Kavazis, et al. (2019). Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 317(3). pp. R397–R406. 10.1152/ajpregu.00110.2019 Retrieved from https://hdl.handle.net/10161/29771.
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Christopher Vann
Dr. Vann is an exercise physiologist with a research focus centered in skeletal muscle physiology. His research focuses on elucidating mechanisms of tissue-to-tissue crosstalk and understanding how exercise-induced changes in epigenetic, genetic, and protein-level factors relate to health and performance outcomes across the age span. As rates of obesity, cardiometabolic disease, and sarcopenia increase in the U.S., Dr. Vann's research is centered on understanding the role of exercise in improved health outcomes at the molecular level and applying this knowledge to develop precise evidence based exercise interventions.
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