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

dc.contributor.author

Mumford, Petey W

dc.contributor.author

Romero, Matthew A

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Osburn, Shelby C

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Roberson, Paul A

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Vann, Christopher G

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Mobley, Christopher B

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Brown, Michael D

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Kavazis, Andreas N

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Young, Kaelin C

dc.contributor.author

Roberts, Michael D

dc.date.accessioned

2024-01-11T17:36:48Z

dc.date.available

2024-01-11T17:36:48Z

dc.date.issued

2019-09-01

dc.description.abstract

<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>

dc.identifier.issn

0363-6119

dc.identifier.issn

1522-1490

dc.identifier.uri

https://hdl.handle.net/10161/29771

dc.language

en

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American Physiological Society

dc.relation.ispartof

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

dc.relation.isversionof

10.1152/ajpregu.00110.2019

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.title

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

dc.type

Journal article

pubs.begin-page

R397

pubs.end-page

R406

pubs.issue

3

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

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Staff

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Institutes and Centers

pubs.organisational-group

Center for the Study of Aging and Human Development

pubs.publication-status

Published

pubs.volume

317

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