Regulatory Role of SIRT1 in Skeletal Muscle Hypertrophy: Molecular Implications
DOI:
https://doi.org/10.35451/k6g79c98Keywords:
SIRT1, Muscle Hypertrophy, Skeletal Muscle, MolecularAbstract
Background: Skeletal muscle hypertrophy is an adaptive process influenced by molecular signals and metabolic conditions. Sirtuin 1 (SIRT1), a NAD-dependent deacetylase, plays a crucial role in regulating skeletal muscle growth and regeneration through its interaction with key pathways such as mTOR, PGC-1?, FOXO, and myogenic factors. Aim: This literature review summarizes the current scientific evidence on the role of SIRT1 in muscle hypertrophy, including its effects on mitochondrial efficiency, oxidative stress reduction, and suppression of catabolic genes such as atrogin-1 and MuRF1. Method: A literature search was conducted using databases such as PubMed, ScienceDirect, and Google Scholar, focusing on articles from the last 10 years. Result: These findings indicate that SIRT1’s effects are highly context-dependent, varying with cellular energy status and external stimuli such as exercise or caloric restriction. Rather than directly inducing hypertrophy, SIRT1 facilitates a favorable cellular environment that enables sustained muscle growth. Conclusion: These insights offer promising potential for the development of molecular-based therapies to preserve or enhance muscle mass, particularly in aging populations or pathological conditions.
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[1] Schiaffino S, Reggiani C, Akimoto T, Blaauw B. Molecular Mechanisms of Skeletal Muscle Hypertrophy. J Neuromuscul Dis [Internet]. 2021 Mar 2;8(2):169–83. Available from: https://journals.sagepub.com/doi/full/10.3233/JND-200568
[2] Flewwelling LD, Hannaian SJ, Cao V, Chaillou T, Churchward-Venne TA, Cheng AJ. What are the potential mechanisms of fatigue-induced skeletal muscle hypertrophy with low-load resistance exercise training? Am J Physiol Physiol [Internet]. 2025 Mar 1;328(3):C1001–14. Available from: https://journals.physiology.org/doi/10.1152/ajpcell.00266.2024
[3] Caserotti P. Strength Training in Older Adults: Changes in Mechanical Muscle Function And Functional Performance. Open Sports Sci J [Internet]. 2014 Mar 7;3(1):62–6. Available from: http://benthamopen.com/ABSTRACT/TOSSJ-3-62
[4] Léger B, Cartoni R, Praz M, Lamon S, Dériaz O, Crettenand A, et al. Akt signalling through GSK‐3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol [Internet]. 2006 Nov 27;576(3):923–33. Available from: https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.2006.116715
[5] Radak Z, Suzuki K, Posa A, Petrovszky Z, Koltai E, Boldogh I. The systemic role of SIRT1 in exercise mediated adaptation. Redox Biol [Internet]. 2020 Aug;35:101467. Available from: https://linkinghub.elsevier.com/retrieve/pii/S221323172030080X
[6] Ryuta N, Hosoda R, Kuno A, Asakura S, Iwahara N, Nojima I, et al. Deletion of SIRT1 in the skeletal muscle causes suppression of autophagy and muscle atrophy. Proc Annu Meet Japanese Pharmacol Soc [Internet]. 2022;95:1-SS-44. Available from: https://www.jstage.jst.go.jp/article/jpssuppl/95/0/95_1-SS-44/_article/-char/ja/
[7] Zheng L, Rao Z, Wu J, Ma X, Jiang Z, Xiao W. Resistance Exercise Improves Glycolipid Metabolism and Mitochondrial Biogenesis in Skeletal Muscle of T2DM Mice via miR-30d-5p/SIRT1/PGC-1α Axis. Int J Mol Sci [Internet]. 2024 Nov 19;25(22):12416. Available from: https://www.mdpi.com/1422-0067/25/22/12416
[8] Chen K, Gao P, Li Z, Dai A, Yang M, Chen S, et al. Forkhead Box O Signaling Pathway in Skeletal Muscle Atrophy. Am J Pathol [Internet]. 2022 Dec;192(12):1648–57. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0002944022002863
[9] Gombos Z, Koltai E, Torma F, Bakonyi P, Kolonics A, Aczel D, et al. Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels. Int J Mol Sci [Internet]. 2021 Jul 15;22(14):7588. Available from: https://www.mdpi.com/1422-0067/22/14/7588
[10] 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 (Basel) [Internet]. 2021 May 5;12(5):691. Available from: https://www.mdpi.com/2073-4425/12/5/691
[11] Juan CG, Matchett KB, Davison GW. A systematic review and meta-analysis of the SIRT1 response to exercise. Sci Rep [Internet]. 2023 Sep 7;13(1):14752. Available from: https://www.nature.com/articles/s41598-023-38843-x
[12] Koltai E, Bori Z, Chabert C, Dubouchaud H, Naito H, Machida S, et al. SIRT1 may play a crucial role in overload‐induced hypertrophy of skeletal muscle. J Physiol [Internet]. 2017 Jun 28;595(11):3361–76. Available from: https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP273774
[13] Davenport AM, Huber FM, Hoelz A. Structural and Functional Analysis of Human SIRT1. J Mol Biol [Internet]. 2014 Feb;426(3):526–41. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022283613006359
[14] Ghosh HS, McBurney M, Robbins PD. SIRT1 Negatively Regulates the Mammalian Target of Rapamycin. Blagosklonny M V., editor. PLoS One [Internet]. 2010 Feb 15;5(2):e9199. Available from: https://dx.plos.org/10.1371/journal.pone.0009199
[15] Woodman KG, Coles CA, Lamandé SR, White JD. Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice. Molecules [Internet]. 2021 Feb 6;26(4):853. Available from: https://www.mdpi.com/1420-3049/26/4/853
[16] Bennett BT, Mohamed JS, Alway SE. Effects of Resveratrol on the Recovery of Muscle Mass Following Disuse in the Plantaris Muscle of Aged Rats. López Lluch G, editor. PLoS One [Internet]. 2013 Dec 12;8(12):e83518. Available from: https://dx.plos.org/10.1371/journal.pone.0083518
[17] Niu W, Wang H, Wang B, Mao X, Du M. Resveratrol improves muscle regeneration in obese mice through enhancing mitochondrial biogenesis. J Nutr Biochem [Internet]. 2021 Dec;98:108804. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0955286321002242
[18] Cetrullo S, D’Adamo S, Tantini B, Borzi RM, Flamigni F. mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management. Crit Rev Eukaryot Gene Expr [Internet]. 2015;25(1):59–75. Available from: http://www.dl.begellhouse.com/journals/6dbf508d3b17c437,4abcfae40adc6398,55208d285e6515e5.html
[19] Gurd B, Williams C. Skeletal muscle SIRT1 and the genetics of metabolic health: therapeutic activation by pharmaceuticals and exercise. Appl Clin Genet [Internet]. 2012 Aug;81. Available from: http://www.dovepress.com/skeletal-muscle-sirt1-and-the-genetics-of-metabolic-health-therapeutic-peer-reviewed-article-TACG
[20] Suwa M, Nakano H, Radak Z, Kumagai S. Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α protein expressions in rat skeletal muscle. Metabolism [Internet]. 2008 Jul;57(7):986–98. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0026049508000887
[21] Luen Tang B. Sirt1 and the Mitochondria. Mol Cells [Internet]. 2016 Feb;39(2):87–95. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1016847823050124
[22] Islam H, Edgett BA, Gurd BJ. Coordination of mitochondrial biogenesis by PGC-1α in human skeletal muscle: A re-evaluation. Metabolism [Internet]. 2018 Feb;79:42–51. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0026049517303037
[23] Hoppeler H. Molecular networks in skeletal muscle plasticity. Lindstedt SL, Hoppeler HH, editors. J Exp Biol [Internet]. 2016 Jan 1;219(2):205–13. Available from: https://journals.biologists.com/jeb/article/219/2/205/33489/Molecular-networks-in-skeletal-muscle-plasticity
[24] Bodine SC. The role of mTORC1 in the regulation of skeletal muscle mass. Fac Rev [Internet]. 2022 Nov 11;11. Available from: https://facultyopinions.com/prime/reports/b/11/32/
[25] Goodman CA. Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass. J Appl Physiol [Internet]. 2019 Aug 1;127(2):581–90. Available from: https://www.physiology.org/doi/10.1152/japplphysiol.01011.2018
[26] Reed SA, Sandesara PB, Senf SM, Judge AR. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J [Internet]. 2012 Mar 18;26(3):987–1000. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.11-189977
[27] Zhao J, Brault JJ, Schild A, Goldberg AL. Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy [Internet]. 2008 Apr 27;4(3):378–80. Available from: http://www.tandfonline.com/doi/abs/10.4161/auto.5633
[28] Li C, Deng Z, Zheng G, Xie T, Wei X, Huo Z, et al. Resveratrol Prevents Skeletal Muscle Atrophy and Senescence via Regulation of Histone Deacetylase 2 in Cigarette Smoke-Induced Mice with Emphysema. J Inflamm Res [Internet]. 2022 Sep;Volume 15:5425–37. Available from: https://www.dovepress.com/resveratrol-prevents-skeletal-muscle-atrophy-and-senescence-via-regula-peer-reviewed-fulltext-article-JIR
[29] Dang K, Li YZ, Gong LC, Xue W, Wang HP, Goswami N, et al. Correction: Stable atrogin-1 ( Fbxo32 ) and MuRF1 ( Trim63 ) gene expression is involved in the protective mechanism in soleus muscle of hibernating Daurian ground squirrels ( Spermophilus dauricus ). Biol Open [Internet]. 2022 Nov 15;11(11). Available from: https://journals.biologists.com/bio/article/11/11/bio059737/285330/Correction-Stable-atrogin-1-Fbxo32-and-MuRF1
[30] Careccia G, Mangiavini L, Cirillo F. Regulation of Satellite Cells Functions during Skeletal Muscle Regeneration: A Critical Step in Physiological and Pathological Conditions. Int J Mol Sci [Internet]. 2023 Dec 29;25(1):512. Available from: https://www.mdpi.com/1422-0067/25/1/512
[31] Dilworth Fj, Blais A. Epigenetic regulation of satellite cell activation during muscle regeneration. Stem Cell Res Ther [Internet]. 2011 Apr 19;2(2):18. Available from: https://stemcellres.biomedcentral.com/articles/10.1186/scrt59
[32] Segalés J, Perdiguero E, Muñoz‐Cánoves P. Epigenetic control of adult skeletal muscle stem cell functions. FEBS J [Internet]. 2015 May 21;282(9):1571–88. Available from: https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13065
[33] Asakura A, Hirai H, Kablar B, Morita S, Ishibashi J, Piras BA, et al. Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle. Proc Natl Acad Sci [Internet]. 2007 Oct 16;104(42):16552–7. Available from: https://pnas.org/doi/full/10.1073/pnas.0708145104
[34] Wang J, Wang F, Zhang P, Liu H, He J, Zhang C, et al. PGC-1α over-expression suppresses the skeletal muscle atrophy and myofiber-type composition during hindlimb unloading. Biosci Biotechnol Biochem [Internet]. 2017 Mar 4;81(3):500–13. Available from: https://academic.oup.com/bbb/article/81/3/500/5938845
[35] Tonkin J, Villarroya F, Puri PL, Vinciguerra M. SIRT1 signaling as potential modulator of skeletal muscle diseases. Curr Opin Pharmacol [Internet]. 2012 Jun;12(3):372–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1471489212000331
[36] Amat R, Planavila A, Chen SL, Iglesias R, Giralt M, Villarroya F. SIRT1 Controls the Transcription of the Peroxisome Proliferator-activated Receptor-γ Co-activator-1α (PGC-1α) Gene in Skeletal Muscle through the PGC-1α Autoregulatory Loop and Interaction with MyoD. J Biol Chem [Internet]. 2009 Aug;284(33):21872–80. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0021925818493933
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