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Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles

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Abstract

In skeletal muscles, calorie restriction (CR) preserves muscle mass in middle-aged rats but not younger rats. The underlying mechanisms for this age-specific response are unknown. Skeletal muscle mass depends on several factors, with protein synthesis and degradation playing major roles. Therefore, the purpose of this study was to investigate whether CR affects younger and older animals differently on mTOR signaling and ubiquitin-proteasome pathway (UPP). Four-, 8-, and 16-month-old rats, with or without 40% CR for a duration of 14 weeks, were sacrificed after an overnight fasting. Total protein content and the phosphorylation level of AKT, mTOR, S6K, and 4EBP1 and protein content of key markers in the UPP (FOXO3a, atrogin, MuRF1, ubiquitinated proteins, proteasome subunits alpha 7 and beta 5) were determined. Unlike younger rats, CR decreased the content of phosphorylated mTOR, S6K, phosphorylated S6K, FOXO3a, and ubiquitinated proteins in middle-aged rats. In conclusion, CR-induced reduction of content/ phosphorylation levels of key proteins in mTOR signaling and the UPP occurred in the middle-aged rats but not younger rats. The age-dependent effects of CR on mTOR signaling and the UPP indirectly explained the age-related effects of CR on muscle mass of animals.

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Acknowledgments

This work was supported by Ministry of Science and Technology (106-2314-B-010 -052 -MY3); and Chang Gung Memorial Hospital (CMPRD3D0213). We thank Yu-Mei Chih for technical assistance and Yu-Chieh Lin for drawing the cartoon pictures.

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Authors and Affiliations

  1. Department of Physical Therapy and Assistive Technology, National Yang-Ming University, 155, Sec. 2, Li-nong St, Taipei, 112, Taiwan

    Chiao-Nan Chen

  2. Department of Exercise and Health Science, College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan

    Yi-Hung Liao

  3. Institute of Sports Sciences, University of Taipei, Taipei, Taiwan

    Shiow-Chwen Tsai

  4. Department of Physical Therapy & Athletic Training, Boston University, Boston, MA, USA

    LaDora V. Thompson

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  1. Chiao-Nan Chen
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Correspondence to Chiao-Nan Chen.

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Chen, CN., Liao, YH., Tsai, SC. et al. Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles. GeroScience 41, 871–880 (2019). https://doi.org/10.1007/s11357-019-00109-8

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  • DOI: https://doi.org/10.1007/s11357-019-00109-8

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