The quest to understand why and how we age has led to numerous lines of investigation that have gradually
converged to consider mitochondrial metabolism as a major player. During mitochondrial respiration a small and variable
amount of the consumed oxygen is converted to reactive species of oxygen (ROS). For many years, these ROS have been
perceived as harmful by-products of respiration. However, evidence from recent years indicates that ROS fulfill important
roles as cellular messengers. Results obtained using model organisms suggest that ROS-dependent signalling may even
activate beneficial cellular stress responses, which eventually may lead to increased lifespan. Nevertheless, when an overload
of ROS cannot be properly disposed of, its accumulation generates oxidative stress, which plays a major part in the
ageing process. Comparative studies about the rates of ROS production and oxidative damage accumulation, have led to
the idea that the lower rate of mitochondrial oxygen radical generation of long-lived animals with respect to that of their
short-lived counterpart, could be a primary cause of their slow ageing rate. A hitherto largely under-appreciated alternative
view is that such lower rate of ROS production, rather than a cause may be a consequence of the metabolic constraints
imposed for the large body sizes that accompany high lifespans. To help understanding the logical underpinning
of this rather heterodox view, herein I review the current literature regarding the mechanisms of ROS formation, with particular
emphasis on evolutionary aspects.
Keywords: Ageing, Lifespan, Mitochondria, OXPHOS, Oxygen, ROS.
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