News and Research: MOTS-c as an exercise mimetic

Study: MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis Nature communications, January 2021


A recent study in the journal Nature communications explains the latest research on a fascinating peptide known as MOTS-c.

Peptides are small molecules made up of 2-50 amino acids.  Proteins are also made up of amino acids, but in chains longer than 50.

Mitochondria are the organelles responsible for energy production in your cells. And mitochondrial health is vital for all aspects of health and wellness – especially in aging.

Your mitochondria contain their own DNA that is separate from your nuclear DNA. But mitchondrial DNA is tiny in comparison to your whole genome — only about 13 protein-coding genes there compared to more than 20,000 in the nucleus.

In addition to the protein-coding genes in the mitochondrial DNA, researchers recently identified short open reading frames (sORFs) that produce bioactive peptides.

One of the mitochondrial peptides is MOTS-c, and researchers are now figuring out that it does a lot…  from regulating nuclear gene expression to promoting healthy metabolism. MOTS-c activates AMPK in skeletal muscles and improves whole body energy metabolism.

The Nature study used cells samples from healthy young males to determine what the normal effects of exercise were on MOTS-c production in muscle cells. The results showed that four hours after exercise, levels of MOTS-c were increased substantially.

Next, the researchers used animals to determine the effect of giving the animals additional MOTS-c.

  • In young animals, giving MOTS-c at a high enough dose effectively reduced weight gain on a fattening diet.
  • In middle-aged and old animals, a two-week treatment with MOTS-c increased physical activity capability by two-fold.
  • In old animals, MOTS-c treatment improved healthspan also.


It is exciting to see the significant effects in animals, and the mechanisms through which the improvement in healthspan occurs.  We are not mice, though, so human trials and specifically randomized-controlled trials are needed to determine if exogenous MOTS-c will be effective in extending healthspan in people.

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.