Lifespan extension by means of dietary restriction is evolutionary conserved yet we do not fully understand its molecular mechanisms. As aging and age-related diseases are growing public health problems, this is an important issue. In this project, we aim to unravel the molecular basis of a specific form of dietary restriction in C. elegans, a common genetic model for studying longevity. Culturing this worm axenically, i.e. in a sterile nutritious medium lacking its normal food source - bacteria, it shows an impressive lifespan doubling. We previously reported that the CREB binding protein CBP-1 is required for ADR-longevity. Recently we identified a second gene involved in this process: the endoprotease bli-4. Using a proteomic approach, we aim to find overlapping or (partially) independent mechanisms by which cbp-1 and bli-4 extend lifespan under axenic dietary restriction (ADR). Finally, we will study how these genes influence not just lifespan but also health under ADR. Therefore, we will quantify the effect of ADR on the onset and intensity of age-related pathologies and study the role of cbp-1 and bli-4 in this process. Overall, this project will provide new insights into mechanisms that drive lifespan extension via dietary restriction, which ultimately may be linked to vertebrate and thus human physiology.