Back to Journals » The Application of Clinical Genetics » Volume 5

Skeletal muscle SIRT1 and the genetics of metabolic health: therapeutic activation by pharmaceuticals and exercise

Authors Williams C, Gurd B

Received 16 May 2012

Accepted for publication 26 June 2012

Published 29 August 2012 Volume 2012:5 Pages 81—91

DOI https://doi.org/10.2147/TACG.S31276

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5


Cameron B Williams, Brendon J Gurd

School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada

Abstract: Silent mating type information regulation 2 homolog 1 (SIRT1) is implicated in the control of skeletal muscle mitochondrial content and function through deacetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and participation in the SIRT1/PGC-1α axis. The SIRT1/PGC-1α axis control of skeletal muscle mitochondrial biogenesis is an important therapeutic target for obesity and obesity-related metabolic dysfunction, as skeletal muscle mitochondrial dysfunction is implicated in the pathogenesis of multiple metabolic diseases. This review will establish the importance of the SIRT1/PGC-1α axis in the control of skeletal muscle mitochondrial biogenesis, and explore possible pharmacological and physiological interventions designed to activate SIRT1 and the SIRT1/PGC-1α axis in order to prevent and/or treat obesity and obesity-related metabolic disease. The current evidence supports a role for therapeutic activation of SIRT1 and the SIRT1/PGC-1α axis by both pharmaceuticals and exercise in the treatment and prevention of metabolic disease. Future research should be directed toward the feasibility of pharmaceutical activation of SIRT1 in humans and refining exercise prescriptions for optimal SIRT1 activation.

Keywords: SIRT1, PGC-1a, resveratrol, obesity, metabolic disease, exercise

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]