Lactate and pyruvate promote cellular stress resistance and longevity through ROS signaling.

L-lactate, for long considered a glycolytic end-product, is now recognized as an important energy substrate. Moreover, it appears that its role is not limited to energy production but also as a signal for neuroprotection and synaptic plasticity. Using a model of neuroblastoma cells and the nematode C. elegans we investigated the cellular mechanisms underlying this protective role of L-lactate. We found that L-lactate promotes a mild Reactive Oxygen Species (ROS) induction that translates into activation of antioxidant defenses and pro-survival pathways such as PI3K/AKT and Endoplasmic Reticulum (ER) chaperones. This hormetic mechanism provides protection against oxidative stress in both cells and nematodes. Furthermore, a mild ROS induction by lactate also promotes longevity in C. elegans.