The Long and the Short of It: How Oxidative Stress Drives Cellular Senescence, Ageing, and Lifespan of Animals

The process of lifetime progressive deterioration in cellular function and organismal performance is what we usually call ageing. Cellular senescence is a form of stable cell cycle arrest that represents a hallmark of ageing, and reactive oxygen species are important triggers of cellular senescence. We have much empirical evidence that ageing occurs in free-living animals, and evolves in connection with life-history strategies. We have a limited understanding of the molecular mechanisms that would drive their ageing. We have evidence that longer-lived species generally have (i) lower generation of reactive oxygen speciesreactive species or oxidative damage, (ii) higher capacity to repair damage, (iii) lower concentrations of endogenous antioxidants, or (iv) cells made of molecules that are more resistant to oxidative damage than shorter-lived species. However, there are a growing number of studies providing contradictory data, raising doubt on the generalisability of the impact of reactive oxygen species on ageing. In this chapter, I have initially presented a general overview of the historical phases that led to the free radical or oxidative stress hypotheses of ageing. Then, I have (i) reviewed the evidence in (dis)favour of the roles of reactive oxygen species and oxidative stress as molecular drivers of cellular senescence and ageing, (ii) discussed under which conditions oxidative stress can be a promoter of longevity, (iii) illustrated how cross-sectional and longitudinal studies of captive or free-living animals do not always support the general hypothesis that oxidative damage and antioxidants should accumulate and decline with age, respectively, and (iv) presented the conflicting results on the link between oxidative status markers and survival probability. In so doing, I critically appraise our current theoretical and methodological approaches, indicating the need for alternative testable hypotheses, and the need to move beyond the oversimplistic and unsupported predictions ‘high oxidative damage at time x is linked to lower survival probability’ and ‘two individuals of the same age showing, e.g. similar levels of a given marker of oxidative damage at time t, should have a similar probability of survival per unit of time’. Regulation of oxidative status homeostasis is a dynamic, continuous, and complex process that needs to be better integrated into the research on cellular senescence and ageing of free-living organisms.