Cancer and ageing: rival demons?

Abstract

Cancer is a problem that affects organisms with renewable tissues; these have evolved tumour-suppressor mechanisms to suppress the development of cancer. Tumour-suppressor genes act to prevent or repair genomic damage (caretakers), or inhibit the propagation of potential cancer cells (gatekeepers) by permanently arresting their growth (cellular senescence) or inducing cell death (apoptosis). Some caretaker tumour suppressors seem to postpone the development of ageing phenotypes, and so are also longevity-assurance genes. The gatekeeper tumour-suppressor mechanisms (apoptosis and cellular senescence), by contrast, might promote certain ageing phenotypes. Apoptosis and cellular senescence are controlled by the p53 and RB tumour-suppressor pathways, components of which are evolutionarily conserved among multicellular organisms. The evolutionary hypothesis of antagonistic pleiotropy predicts that some processes that benefit young organisms (by suppressing cancer, for example) can have detrimental effects later in life and would therefore contribute to ageing. Both apoptosis and cellular senescence might be antagonistically pleiotropic, promoting ageing by exhausting progenitor or stem cells. Additionally, senescent cells secrete factors that can disrupt tissue integrity and function, and even promote the progression of late-life cancers. Recent studies on p53 provide a molecular basis for how tumour suppression and ageing might be intertwined.