Obesity and aging are two of the most important health challenges facing our societies in the 21st century. However, there are currently no effective therapeutic approaches to mitigate the growing obesity pandemic or to promote healthy aging. Therefore, it is essential to explore new research frontiers in order to develop more effective and safer strategies. Mitohormesis, the process by which induced mitochondrial stress can trigger beneficial health effects, has emerged as a promising area of study in biomedical research. However, its potential effectiveness against metabolic and aging-associated disorders in vertebrate organisms is poorly explored. We have generated a mouse model that exhibits enhanced mitohormesis in the vascular endothelial cells. In this proposal, we intend to conduct a proof of concept to assess whether triggering endothelial mitohormesis can serve as a novel approach for treating obesity and age-related health issues. To this aim, we will execute 4 work packages to determine: (a) the preventive and (b) curative effect of endothelial mitohormesis on obesity and associated metabolic alterations; (c) the impact of the promotion of endothelial mitohormesis on aging markers; (d) the identity of new circulating mitohormetic mediators with the potential to be pharmacological targets. These studies will be carried out by a research team with an extraordinary track-record in the fields of metabolism and aging. Our objective will be bringing the technology from TRL3 to TRL4 by evaluating the performance and feasibility of the technology in a controlled laboratory environment. The research team will closely work with the Tech Transfer Office to ensure the implementation of a successful IPR strategy. A therapy based on the controlled induction of endothelial mitohormesis could have a great impact on the quality of life of millions of patients, reduce the burden of chronic diseases on the health system and have important economic repercussions.