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Updated: May 5, 2026
Activating Autophagy by Aerobic Exercise in Mice
Published on: February 3, 2017
Exercise training can induce cardiac autophagy at end-stage chronic conditions: insights from a
Carmen Fiuza-Luces1, Aitor Delmiro2, Luisa Soares-Miranda3
1European University and Hospital Universitario 12 de Octubre Research Institute (i+12), Madrid, Spain.
Insights
Exercise training improved cardiac function in a mouse model of chronic graft-versus-host disease (cGVHD) by enhancing autophagy. This cellular process may preserve heart function in debilitating conditions.
Area of Science:
- Cardiovascular Physiology
- Exercise Science
- Cellular Biology
Background:
- Chronic graft-versus-host disease (cGVHD) significantly impairs physical capacity post-allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- Aerobic exercise training shows potential to improve survival and functional parameters in cGVHD patients.
- Autophagy, a cellular quality-control mechanism, is being investigated for its role in disease adaptation and recovery.
Purpose of the Study:
- To investigate the role of autophagy in exercise-induced cardiac function improvement in a cGVHD murine model.
- To analyze molecular mechanisms underlying cardiac benefits of exercise in cGVHD.
Main Methods:
- BALB/C mice with cGVHD underwent 11 weeks of moderate-intensity treadmill training.
- Cardiac tissue was analyzed for markers of macroautophagy, protein preservation, oxidative capacity, oxidative stress, antioxidant defense, and mitochondrial dynamics.
- Key molecular markers were quantified in surviving mice.
Main Results:
- Exercise training significantly increased myocardial macroautophagy markers (LC3BII, Atg12, SQSTM1/p62, phospho-ULK1).
- Exercise also enhanced levels of contractile proteins (α-tubulin) and antioxidant enzymes (catalase, glutathione reductase).
- These molecular adaptations suggest improved cellular maintenance and reduced oxidative stress.
Conclusions:
- Exercise training induces beneficial autophagic adaptation in the heart during cGVHD.
- This autophagic response may contribute to preserving cardiac function in advanced stages of cGVHD.
- Findings suggest exercise may offer therapeutic benefits for cardiac dysfunction in chronic and debilitating diseases.
Introduction:
Chronic graft-versus-host disease (cGVHD) is a frequent cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and severely compromises patients' physical capacity. Despite the aggressive nature of the disease, aerobic exercise training can positively impact survival as well as clinical and functional parameters. We analyzed potential mechanisms underlying the recently reported cardiac function improvement in an exercise-trained cGVHD murine model receiving lethal total body irradiation and immunosuppressant treatment (Fiuza-Luces et al., 2013. Med Sci Sports Exerc 45, 1703-1711). We hypothesized that a cellular quality-control mechanism that is receiving growing attention in biomedicine, autophagy, was involved in such improvement.
Methods:
BALB/C female mice (aged 8wk) with cGVHD were randomly assigned to a control/exercise group (n=12/11); the exercise group underwent moderate-intensity treadmill training during 11wk after allo-HSCT. In the hearts of those few mice surviving the entire 11wk period (n=2/5), we studied molecular markers of: macroautophagy induction, preservation of contractile/structural proteins, oxidative capacity, oxidative stress, antioxidant defense, and mitochondrial dynamics.
Results:
Mainly, exercise training increased the myocardial content of the macroautophagy markers LC3BII, Atg12, SQSTM1/p62 and phospho-ULK1 (S555), as well as of α-tubuline, catalase and glutathione reductase (all p<0.05).
Conclusions:
Our results suggest that exercise training elicits a positive autophagic adaptation in the myocardium that may help preserve cardiac function even at the end-stage of a devastating disease like cGVHD. These preliminary findings might provide new insights into the cardiac exercise benefits in chronic/debilitating conditions.
