The Gut-Extracellular Vesicle-Mitochondria Axis in Reproductive Aging: Antioxidant and Anti-Senescence Mechanisms.

Authors

Efthalia Moustakli, Christina Messini, Anastasios Potiris, Athanasios Zikopoulos, Ioannis Arkoulis, Alexios Kozonis, Theodoros Karampitsakos, Pavlos Machairoudias, Nikolaos Machairiotis, Panagiotis Antsaklis, Periklis Panagopoulos, Sofoklis Stavros, Ekaterini Domali

Published in

Antioxidants (Basel, Switzerland). Volume 15. Issue 2. Jan 28, 2026. Epub Jan 28, 2026.

Abstract

Cellular senescence, mitochondrial dysfunction, and cumulative oxidative stress (OS) are the main causes of the progressive decreases in oocyte and sperm quality that define reproductive age. There is growing evidence that these processes are controlled by systemic variables, such as metabolites produced from the gut microbiome and extracellular vesicle (EV)-mediated intercellular communication, rather than being exclusively regulated at the tissue level. Antioxidant enzymes, regulatory microRNAs, and bioactive lipids that regulate mitochondrial redox balance, mitophagy, and inflammatory signaling are transported by EVs derived from reproductive organs, stem cells, immune cells, and the gut microbiota. Concurrently, microbiome-derived metabolites such as urolithin A, short-chain fatty acids, and polyphenol derivatives enhance mitochondrial quality control, activate antioxidant pathways, and suppress senescence-associated secretory phenotypes. This narrative review integrates the most recent research on the relationship between redox homeostasis, mitochondrial function, gut microbiota activity, and EV signaling in the context of male and female reproductive aging. We propose an emerging gut-EV-mitochondria axis as a unified framework through which systemic metabolic and antioxidant signals affect gamete competence, reproductive tissue function, and fertility longevity. Finally, we discuss therapeutic implications, including microbiome modulation, EV-based interventions, and senotherapeutic strategies, highlighting key knowledge gaps and future research directions necessary for clinical translation.

PMID:
41750555
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.