MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Summary

Mostly an animal (mouse) study, with cell experiments and human exercise measurements. The authors report that MOTS-c, a peptide encoded in the mitochondrial genome, significantly enhanced physical performance in young (2 months), middle-aged (12 months), and old (22 months) mice, and that intermittent treatment started late in life (23.5 months, 3x/week) increased physical capacity and healthspan. In humans, exercise increased endogenous MOTS-c in skeletal muscle and in circulation; MOTS-c was not given to people in this study.

Key Findings

• MOTS-c significantly enhanced physical performance in young, middle-aged, and old mice
• MOTS-c regulated nuclear genes, including genes related to metabolism and proteostasis
• MOTS-c regulated skeletal muscle metabolism and myoblast adaptation to metabolic stress
• Late-life (23.5 months) intermittent MOTS-c treatment (3x/week) increased physical capacity and healthspan in mice
• Exercise induced endogenous MOTS-c expression in human skeletal muscle and in circulation
• The authors conclude that aging is regulated by genes encoded in both the mitochondrial and nuclear genomes

Methodology

MOTS-c was administered to mice of three ages and physical performance was assessed; a late-life cohort received intermittent treatment (3x/week) starting at 23.5 months. Effects on nuclear gene expression, skeletal muscle metabolism, and myoblast responses to metabolic stress were examined. In humans, endogenous MOTS-c was measured in skeletal muscle and blood in response to exercise. The abstract does not give group sizes, doses, or treatment duration.

Limitations

• Performance and healthspan effects come from mice and may not translate to humans
• The human component measured the body’s own MOTS-c response to exercise; it did not test MOTS-c administration
• Sample sizes, doses, and treatment length are not stated in the abstract
• The authors (P.C. and C.L.) disclosed that they are consultants and shareholders of CohBar, Inc.

Relevance to Content

This is the main animal study behind claims that MOTS-c counters age-related physical decline and acts as an exercise-linked mitochondrial signal. Content should present the performance and healthspan results as mouse findings, and the human result as evidence that exercise raises endogenous MOTS-c, not that injected MOTS-c improves human performance.

See Also

• Parent compound: MOTS-c