nor lead to an increase in the number of epithelial tumours. Instead, the late-generation Terc−/− Ink4a/Arf−/− mice succumbed to the lymphoma and sarcoma spectrum expected for Ink4a/Arf−/− mice, albeit with a longer latency77. These contrasting studies not only underscore how the genetic context can dramatically dictate the role of telomeres in ageing and cancer but also pinpoint the importance of p53, as the preservation of DNA-damage-induced signalling and p53 activation may underlie the lack of a rescue with Ink4a/Arf deficiency77. Indeed, p53 activation and associated increased apoptosis has been documented in tissues of lategeneration Terc−/− Ink4a/Arf −/− mice that show testicular and intestinal atrophy, as well as impaired haematopoiesis77. Whether these defects are specifically associated with depletion of tissue stem cells is not yet known, but they warrant further investigation.
