Research Paper Volume 12, Issue 6 pp 5244—5258
Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition
- 1 Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- 2 Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
- 3 Liggins Institute, The University of Auckland, Auckland, New Zealand
- 4 Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- 5 Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
- 6 Japan Society for the Promotion of Science, Tokyo, Japan
- 7 Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan
- 8 USC Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA
- 9 Biomedical Science, Graduate School, Ajou University, Suwon, Korea
- 10 School of Kinesiology, University of British Colombia, Vancouver, BC V6T 1Z1, Canada
Received: December 21, 2019 Accepted: March 9, 2020 Published: March 17, 2020https://doi.org/10.18632/aging.102944
How to Cite
Copyright © 2020 D’Souza et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mitochondria putatively regulate the aging process, in part, through the small regulatory peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) that is encoded by the mitochondrial genome. Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men. Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had ~1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y). Plasma MOTS-c levels only correlated with plasma in young men, was associated with markers of slow-type muscle, and associated with improved muscle quality in the older group (maximal leg-press load relative to thigh cross-sectional area). Using small mRNA assays we provide evidence that MOTS-c transcription may be regulated independently of the full length 12S rRNA gene in which it is encoded, and expression is not associated with antioxidant response element (ARE)-related genes as previously seen in culture. Our results suggest that plasma and muscle MOTS-c are differentially regulated with aging, and the increase in muscle MOTS-c expression with age is consistent with fast-to-slow type muscle fiber transition. Further research is required to determine the molecular targets of endogenous MOTS-c in human muscle but they may relate to factors that maintain muscle quality.