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SCI 20 December 2024 Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis (Nature; IF:50.5) Correspondence to：tammelat@mskcc.org Zhuang X, Wang Q, Joost S, Ferrena A, Humphreys DT, Li Z, et al. Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis. Nature. 2024 Abstract 摘要 Ageing is associated with a decline in the number and fitness of adult stem cells. Ageing-associated loss of stemness is posited to suppress tumorigenesis, but this hypothesis has not been tested in vivo. Here we use physiologically aged autochthonous genetically engineered mouse models and primary cells to demonstrate that ageing suppresses lung cancer initiation and progression by degrading the stemness of the alveolar cell of origin. This phenotype is underpinned by the ageing-associated induction of the transcription factor NUPR1 and its downstream target lipocalin-2 in the cell of origin in mice and humans, which leads to functional iron insufficiency in the aged
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