Reynolds · Nature communications 2021 · Preclinical animal and cell study with human exercise biomarker analysis · n=?

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

Cited 192 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical animal and in vitro experiments with human observational biomarker measurement.

PubMed 33473109 · doi:10.1038/s41467-020-20790-0 · record verified 2026-08-27

What was done

Researchers evaluated the effect of the mitochondrial-derived peptide MOTS-c on physical performance, skeletal muscle metabolism, and myoblast adaptation in young (2 months), middle-aged (12 months), and old (22 months) mice. They also administered intermittent MOTS-c (3 times per week) starting at late life (23.5 months) in mice to assess healthspan and physical capacity. In humans, endogenous MOTS-c expression was measured in skeletal muscle and circulation following exercise.

What was found

MOTS-c administration enhanced physical performance across young, middle-aged, and old mice and regulated nuclear gene networks related to metabolism and proteostasis. Late-life intermittent treatment increased physical capacity and healthspan in mice. In humans, exercise induced endogenous MOTS-c expression in both skeletal muscle and circulation. The abstract does not provide exact numerical effect sizes, confidence intervals, or sample sizes.

Why it matters

This work identifies a mitochondrial-encoded peptide as an active regulator of muscle metabolism and aging-related physical capacity, suggesting a biological mediator for the beneficial systemic effects of exercise.

Limits

The abstract reports no sample sizes for the mouse cohorts or human subjects, nor does it provide quantitative effect estimates or statistical variance. Findings regarding healthspan and physical performance rescue are restricted to mouse models, and human data are limited to correlational expression changes following exercise rather than interventional peptide administration.

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