The cancer-ageing hypothesis suggests that the activation of some tumor suppressor mechanisms beneficially prevent cancer but also untowardly promote mammalian ageing. Along these lines, activation of tumor suppressor mechanisms that inhibit the cell cycle (e.g. p16INK4a and p53) in response to DNA damage and other age-promoting stimuli have taken center stage in immune-ageing research. Immune cells are intrinsically susceptible to transforming events due to V(D)J recombination, a high rate of cellular turnover and requisite long-term self-renewal. Therefore, the DNA damage response and cell cycle regulation play a clear role in maintaining homeostasis without neoplastic progression. Here we will argue based on recent advances in our understanding of tumor suppressor mechanisms in immune cells, however, that aspects of these same beneficial pathways have the potential to induce intrinsic immune ageing
