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Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review

A summary of earlier studies · Physiology international · Aug 25, 2026

What this means

Type 2 diabetes mellitus and metabolic diseases are increasing worldwide and are closely linked to mitochondrial dysfunction. Mitochondrial-derived peptides (MDPs), such as humanin and MOTS-c, play a role in regulating energy balance and cellular stress responses.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inSummary of earlier studies
Who it was tested in
People
Kind of research
A summary of earlier studies

The science

Original title
Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review.
Authors
Ayubi N, Wibawa JC, Kurnaz M et al.
Journal
Physiology international
Published
Aug 25, 2026
Study type
Review · in humans

Abstract

Background

Type 2 diabetes mellitus and metabolic diseases are increasing worldwide and are closely linked to mitochondrial dysfunction. Mitochondrial-derived peptides (MDPs), such as humanin and MOTS-c, play a role in regulating energy balance and cellular stress responses. Exercise is known to improve metabolic function and stimulate MDP synthesis through mitochondria-dependent signaling pathways. Understanding these mechanisms has the potential to uncover new therapeutic targets for the treatment of metabolic diseases.

What they did

This systematic review searched four electronic databases, PubMed, Scopus, Web of Science, and ScienceDirect, for studies published between 2016 and 2025 that examined MDPs and exercise. A total of 435 records were identified. After screening according to predefined inclusion and exclusion criteria following PRISMA guidelines, nine studies were included in the final analysis.

What they found

Of the nine studies included in this systematic review, most reported a trend toward increased MDP levels after exercise. However, these findings should be interpreted with caution due to the limited number of studies and variations in study design, subject characteristics, and exercise protocols. Available evidence suggests that physical exercise has the potential to increase MDP levels, which may be associated with improved metabolic function, increased insulin sensitivity, and the efficiency of cellular energy metabolism. However, current evidence is limited, particularly in human studies. Therefore, further research, particularly controlled clinical trials and longitudinal studies, is needed to confirm these findings and evaluate MDP's potential as a therapeutic target in the prevention and management of metabolic diseases.

Other details

This study sought to ascertain how physical activity affected MDPs levels.

The authors' abstract, grouped under plain headings from its own section labels.

Read it on PubMed ↗

Ayubi N, Wibawa JC, Kurnaz M et al. Mitochondrial-derived peptides (MDPs) activated by physical exercise as therapeutic targets for metabolic disorders: A systematic review. Physiology international. 2026. doi:10.1556/2060.2026.00863. PMID: 42640735. https://pubmed.ncbi.nlm.nih.gov/42640735/

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