Mouse study: exercise limited doxorubicin-induced cardiac senescence via irisin
In p16-3MR mice, doxorubicin reduced cardiac function and raised senescent cell markers; these changes were not seen with doxorubicin plus exercise. Cell studies suggested irisin may mediate this. [1]
Automatic summary · not editorially reviewed
The key findings
In p16-3MR mice, doxorubicin decreased cardiac function and increased p16INK4a-positive and beta-galactosidase-positive senescent cells in the heart. [1]
According to the abstract, these changes were not seen in mice treated with doxorubicin plus exercise. [1]
In vitro studies with human cardiomyocytes and endothelial cells confirmed that irisin attenuated doxorubicin-induced senescence. [1]
The source at a glance
- Study type / format
- Preclinical mouse experiment plus in vitro cell studies (abstract)
- Population / context
- p16-3MR transgenic mice and, in vitro, human cardiomyocytes and endothelial cells
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- September 29, 2026
Doxorubicin effects in p16-3MR mice
The abstract describes a mouse experiment using p16-3MR transgenic mice to study doxorubicin's effect on cardiac senescence. Mice given doxorubicin had decreased cardiac function and more p16INK4a-positive and beta-galactosidase-positive senescent cells in the heart. They also showed decreased HMGB1 and calreticulin expression, endothelial cell senescence, and decreased TUJ1 expression, which the authors say indicates reduced axonal density. Expression of Semaphorin3A and phosphorylated cofilin rose, with impaired F-actin depolarization and cytoskeleton disorganization.
Supporting source [1]
Exercise group and irisin link in the abstract
According to the abstract, none of these changes were seen in mice treated with doxorubicin plus exercise. Exercise sustained cardiac FNDC5 levels compared with doxorubicin-treated hearts, which the authors describe as a suggested link between exercise, decreased senescence and the FNDC5/irisin pathway. In vitro studies with human cardiomyocytes and endothelial cells confirmed that irisin attenuated doxorubicin-induced senescence. The authors conclude that exercise mitigates doxorubicin-induced cardiotoxicity by suppressing cardiovascular senescence via a mechanism involving the exercise-induced myosin irisin, and call exercise a potential intervention for preventing doxorubicin-induced cardiotoxicity.
Supporting source [1]
Abstract-only scope of the mouse and cell findings
This explainer is based only on the abstract; the full text was not reviewed. The abstract does not report sample sizes, exercise details, follow-up duration or statistical measures. The mouse findings are preclinical, and the irisin results come from in vitro studies with human cardiomyocytes and endothelial cells, not from human lifespan or clinical outcome data. The proposed mechanism involving irisin is described as a suggested link, and the statement that exercise is a potential intervention is the authors' interpretation, not a demonstrated treatment.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Sample sizes, exercise protocol, follow-up and statistics are not reported. Mouse and cell findings are preclinical and do not show human lifespan or clinical benefits.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Jeyabal P, Shrestha P, Yang Y, Wang F, Peng Z, Zhou Y, Zheng Y, Kleinerman ES. · europepmc.org · September 29, 2026