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Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Ham, Daniel J. and Börsch, Anastasyia and Chojnowska, Kathrin and Lin, Shuo and Leuchtmann, Aurel B. and Ham, Alexander S. and Thürkauf, Marco and Delezie, Julien and Furrer, Regula and Burri, Dominik and Sinnreich, Michael and Handschin, Christoph and Tintignac, Lionel A. and Zavolan, Mihaela and Mittal, Nitish and Rüegg, Markus A.. (2021) Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle.

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Abstract

As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of "CR mimetics" has received much attention. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, has been proposed as a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our expectation, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Ham, Daniel Jacob and Börsch, Anastasiya and Chojnowska, Kathrin and Lin, Shuo and Leuchtmann, Aurel and Ham, Alexander Sebastian and Thürkauf, Marco and Delezie, Julien and Furrer, Regula and Burri, Dominik and Sinnreich, Michael and Handschin, Christoph and Tintignac, Lionel and Zavolan, Mihaela and Mittal, Nitish and Rüegg, Markus A.
Item Type:Preprint
Publisher:bioRxiv
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
Language:English
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Last Modified:21 May 2022 03:10
Deposited On:03 Mar 2022 15:53

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