Exercise protects mouse hearts from chemotherapy toxicity by suppressing cellular senescence
Physical activity preserved cardiac function and sustained FNDC5 and irisin signaling in mice exposed to doxorubicin.
Research Square · Jeyabal P et al. · Paper published 29 Sep 2026
In a preprint study using p16-3MR transgenic mice, researchers evaluated whether exercise prevents heart damage caused by doxorubicin. Mice treated with the chemotherapy drug developed reduced cardiac function alongside elevated p16INK4a and beta-galactosidase markers of senescent cells in the heart. Doxorubicin also triggered endothelial cell senescence, reduced axonal density, decreased HMGB1 and calreticulin expression, and disrupted the cytoskeleton through Semaphorin3A and phosphorylated cofilin. Concurrent exercise completely prevented these detrimental changes and maintained cardiac levels of FNDC5. In cell culture experiments, treating human cardiomyocytes and endothelial cells with irisin directly attenuated doxorubicin-induced senescence. The findings show that exercise mitigates cardiotoxicity by curbing cardiovascular senescence via FNDC5 and irisin signaling pathways.
Why it matters
The findings link exercise-induced factor signaling to the suppression of acute therapy-driven cardiovascular senescence. Understanding this axis could inform interventions to protect the heart against accelerated tissue aging during chemotherapy.
Caveats
This study is a preprint that has not yet completed peer review. Most findings are limited to mice and cultured cells, requiring confirmation in clinical human settings.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Exercise inhibits doxorubicin-induced cardiotoxicity by preventing cardiac and endothelial cell senescence by activating FNDC5/Irisin signaling
Jeyabal P, Shrestha P, Yang Y et al.
Research Square · 29 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Animals
- Status
- Preprint
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