Early life exercise impacts physiology and lifespan in a sex- and genotype-dependent manner in a Drosophila melanogaster exercise model

Exercise is a common strategy for disease prevention or management, including for diabetes and cardiac dysfunction. However, exercise response varies immensely between individuals, and in humans, the same exercise treatment can lead both to positive and negative responses. Drosophila melanogaster is an established model for exercise research that can be leveraged to understand this variation in exercise response. Here, we investigated how two early life exercise treatments differing in duration (5 and 20 days) impact the animal's health- and lifespan in four genotypes. Specifically, we measured lifespan, activity level, body condition, physical ability, and reproductive output in this exploratory study to gain insights into potential trade-offs. For most measures, we found both immediate and long-term effects, with some effects persisting weeks past the cessation of exercise. The effect of the exercise treatment was context-dependent, with treatment, sex, and genotype interactions determining phenotypes. For example, the 20-day treatment did not exhibit a consistently larger effect than the 5-day treatment. Similarly, neither the 5-day nor the 20-day treatment impacted lifespan, but in two specific genotype/sex combinations showed altered lifespan after exercise. The 20-day treatment decreased climbing performance compared to controls up to several weeks after treatment ended in some genotypes. Together, our results highlight the complex, interacting factors controlling exercise response and demonstrate that early life exercise can have long-lasting effects in the Drosophila exercise model even though most individual groups show no response.