While stem cell fitness declines with age, possibly suppressing tumorigenesis, the increasing risk of cancer with ageing highlights the complexity of this interaction. Now, Zhuang et al. outline how ageing affects the stemness and tumorigenic potential of tumour-initiating alveolar stem cells, AT2 cells, in the lung.

The authors analysed AT2 and LUAD cell transcriptomes at 4-, 12- and 17-weeks post tumour initiation, finding an age-dependent correlation between differentially expressed genes (DEGs) in AT2 and LUAD cells. Gene set enrichment analysis found consistent induction of genes involved in iron homeostasis in aged mice, with nuclear protein transcription regulator 1 (Nupr1) as the most differentially expressed gene. Inactivation of Nupr1 12 weeks after tumour initiation suppressed tumorigenesis in young mice. By contrast, loss of Nupr1 in aged mice led to progression of LUAD.