Oxidative stress and cell senescence as drivers of ageing: Chicken and egg

Oxidative stress and cell senescence are both important drivers of ageing and age-associated disease and disability. In vitro, they are closely interconnected in a chicken-and-egg relationship: Not only is oxidative stress an important cause of cell senescence, but senescent cells are also sources of oxidative stress, obscuring cause-effect relationships during the ageing process. We hypothesize that cell senescence is a significant cause of tissue and systemic oxidative stress during ageing. This review aims to critically summarize the available evidence for this hypothesis. After summarizing the cellular feedback mechanisms that make oxidative stress an integral part of the senescent phenotype, it critically reviews the existing evidence for a role of senescent cells as causes of oxidative stress during mammalian ageing in vivo, focussing on results from intervention experiments. It is concluded that while the available data are in agreement with this hypothesis, they are still too scarce to support a robust conclusion.