Skeletal Muscle Gene Expression Profile in Response to Caloric Restriction and Aging: A Role for SirT1
1
Laboratory of Muscle Biology and Sarcopenia, Division of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, WV 26506, USA
2
Biochemistry and Cellular and Molecular Biology Program, University of Tennessee, Knoxville, TN 37996, USA
3
Laboratory of Muscle Biology and Sarcopenia, Department of Physical Therapy, College of Health, Professions, University of Tennessee Health Science Center, Memphis, TN 38163, USA
4
Center for Muscle, Metabolism, and Neuropathology, Division of Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN 38163, USA
5
Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Author to whom correspondence should be addressed.
†
These authors have equally contributed to this study.
Academic Editor: Mariarosa Anna Beatrice Melone
Genes 2021, 12(5), 691; https://doi.org/10.3390/genes12050691
Received: 6 March 2021
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Revised: 25 April 2021
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Accepted: 29 April 2021
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Published: 5 May 2021
(This article belongs to the Section Molecular Genetics and Genomics)
SirT1 plays a crucial role in the regulation of some of the caloric restriction (CR) responsive biological pathways. Aging suppresses SirT1 gene expression in skeletal muscle, suggesting that aging may affect the role of CR in muscle. To determine the role of SirT1 in the regulation of CR regulated pathways in skeletal muscle, we performed high-throughput RNA sequencing using total RNA isolated from the skeletal muscles of young and aged wild-type (WT), SirT1 knockout (SirT1-KO), and SirT1 overexpression (SirT1-OE) mice fed to 20 wk ad libitum (AL) or 40% CR diet. Our data show that aging repressed the global gene expression profile, which was restored by CR via upregulating transcriptional and translational process-related pathways. CR inhibits pathways linked to the extracellular matrix and cytoskeletal proteins regardless of aging. Mitochondrial function and muscle contraction-related pathways are upregulated in aged SirT1 KO mice following CR. SirT1 OE did not affect whole-body energy expenditure or augment skeletal muscle insulin sensitivity associated pathways, regardless of aging or diet. Overall, our RNA-seq data showed that SirT1 and CR have different functions and activation of SirT1 by its activator or exercise may enhance SirT1 activity that, along with CR, likely have a better functional role in aging muscle.
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Keywords:
sirtuin1; RNA-sequencing; transcriptome; caloric restriction; SirT1 knockout mice; SirT1 transgenic mice; aging
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MDPI and ACS Style
Myers, M.J.; Shaik, F.; Shaik, F.; Alway, S.E.; Mohamed, J.S. Skeletal Muscle Gene Expression Profile in Response to Caloric Restriction and Aging: A Role for SirT1. Genes 2021, 12, 691. https://doi.org/10.3390/genes12050691
AMA Style
Myers MJ, Shaik F, Shaik F, Alway SE, Mohamed JS. Skeletal Muscle Gene Expression Profile in Response to Caloric Restriction and Aging: A Role for SirT1. Genes. 2021; 12(5):691. https://doi.org/10.3390/genes12050691
Chicago/Turabian StyleMyers, Matthew J., Fathima Shaik, Fahema Shaik, Stephen E. Alway, and Junaith S. Mohamed. 2021. "Skeletal Muscle Gene Expression Profile in Response to Caloric Restriction and Aging: A Role for SirT1" Genes 12, no. 5: 691. https://doi.org/10.3390/genes12050691
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