At AgeisBio, we are pioneering research into the biology of aging with a focus on the mechanisms of cell signaling, including oxidative signaling.  In our studies, we evaluated oxidative signaling by simulating both normal physiological conditions and aging and degenerative disease conditions using in vitro cell culture models.  Under healthy and youthful physiological conditions, activities such as exercise, caloric restriction and cold shock, induce homeostatic oxidative signaling in the form of transient increases in reactive oxygen species (ROS).  These ROS act as signaling molecules in key transduction signaling pathways, which effectively initiate stress-induced transcriptional reprogramming to produce cytoprotective proteins that improve overall cellular health.  

In aging, overproduction and accumulation of ROS leads to impaired oxidative signaling as evidenced by the prevalence of excessive ROS in aging and neurodegenerative diseases.  Conventional approaches in redox biology attempt to discover mechanisms that activate the antioxidant transcription factor (Nrf2) to increase antioxidant capacity and reduce excess ROS.  These approaches have proven ineffective, if not detrimental, since they remove ROS and impede its essential role in mediating stress-induced transcriptional reprogramming.  

Our hypothesis in aging is that impaired oxidative signaling dysregulates the cellular stress response and disrupts stress-induced transcriptional reprogramming.  We discovered a target pathway to restore homeostatic oxidative signaling, regulate the stress response, and re-establish effective stress-induced transcriptional reprogramming.  With this, we present a new paradigm in redox biology with an aim to regulate oxidative signaling for its use in effective mediation of the stress response.