Octopamine Drives Endurance Exercise Adaptations in Drosophila

Abstract

Endurance exercise is an effective therapeutic inter- vention with substantial pro-healthspan effects. Male Drosophila respond to a ramped daily program of exercise by inducing conserved physiological re- sponses similar to those seen in mice and humans. Female flies respond to an exercise stimulus but do not experience the adaptive training response seen in males. Here, we use female flies as a model to demonstrate that differences in exercise response are mediated by differences in neuronal ac- tivity. The activity of octopaminergic neurons is spe- cifically required to induce the conserved cellular and physiological changes seen following endurance training. Furthermore, either intermittent, scheduled activation of octopaminergic neurons or octopamine feeding is able to fully substitute for exercise, confer- ring a suite of pro-healthspan benefits to sedentary Drosophila. These experiments indicate that octop- amine is a critical mediator of adaptation to endur- ance exercise in Drosophila.