4.6 Article

Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition

Journal

AGING-US
Volume 12, Issue 6, Pages 5244-5258

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.102944

Keywords

muscle; mitochondria; mitochondrial derived peptides; aging; MOTS-c

Funding

  1. Marsden Fast-start grant
  2. University of Auckland Faculty Research Development Fund
  3. AFAR BIG AWARD [P01AG034906]
  4. Rutherford Discovery Fellowship
  5. NIA [R01AG052258]
  6. Ellison Medical Foundation
  7. AFAR
  8. Hanson-Thorell Family

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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 similar to 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.

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