PMID-33473109 – MOTS-c: Exercise-Induced Regulator of Age-Dependent Physical Decline
Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis," Nature Communications, 2021;12(1):470. doi:10.1038/s41467-020-20790-0
Quick Reference
| Property | Value |
|---|---|
| PMID | 33473109 |
| DOI | 10.1038/s41467-020-20790-0 |
| Year | 2021 |
| Journal | Nature Communications |
| Study Type | Animal in vivo + Human observational |
| Evidence Level | III |
| Sample | Young, middle-aged, and old mice + human exercise cohort |
| Peptide(s) Studied | MOTS-C |
Key Findings
- MOTS-c treatment significantly enhanced physical performance in young, middle-aged, AND old mice
- Late-life MOTS-c treatment (initiated at 23.5 months) reversed age-dependent physical decline
- Exercise induces endogenous MOTS-c expression in skeletal muscle and circulation in both mice and humans
- MOTS-c improved muscle homeostasis and metabolic function in aged animals
- Human component: exercise upregulates MOTS-c in skeletal muscle (observational cohort)
Study Design
Multi-component: (1) MOTS-c IP injection in mice at different life stages with physical performance testing; (2) Muscle transcriptomics and metabolomics; (3) Human exercise cohort measuring MOTS-c levels in skeletal muscle biopsies pre/post exercise.
Limitations
- Mouse intervention data; human component is observational only (no MOTS-c administration in humans)
- Late-life intervention window not tested across full lifespan
- Dosing may not translate directly to human protocols
Clinical Relevance
Landmark study from the Lee lab (MOTS-c discoverer). The combination of mouse intervention and human observational data provides the strongest translational evidence for MOTS-c as an exercise mimetic. The late-life efficacy finding is particularly relevant for anti-aging and sarcopenia applications. Published in Nature Communications (high-impact). Evidence Level III due to the human observational component.
Related
#research #animal-in-vivo #evidence-level-III