Final Report Summary - COMPLEXI&AGING (Modulation of mitochondrial complex I as a strategy to increase lifespan and prevent age-related diseases)
Firstly, we have found that ageing causes the accumulation of respiratory-deficient mitochondria that generate high levels of ROS. Interestingly CI is the first respiratory complex whose function fails and the most affected during ageing. Accordingly, restoring CI function extends lifespan in fruit flies.
Secondly, we have investigated in detail the role of ROS in ageing dissecting by which mechanism CI produces ROS in vivo. We have demonstrated that non-specific induction of ROS causes the accumulation of respiratory-deficient mitochondria and shortens lifespan in young flies. However, site-specific generation of ROS by inducing reverse electron transport at respiratory CI protects mitochondrial function and extends lifespan.
Our results indicate that the SITE where ROS are generated is essential to determine their physiological effects and invites to reconsider the present paradigm describing how ROS operate in vivo. We expect to use this new knowledge to find new therapies to prevent, delay or reverse ageing and the onset of age-related diseases.