In all cases (besides individuals with IBD), TIFAsome formation correlated with age (Extended Data Fig. 6d and Supplementary Table 5), suggesting that circulating ADP-heptose occurs after ageing and reaches levels in individuals with CHIP or with MDS sufficient to activate ALPK1 in pre-leukaemic cells. The gene discussed is ALPK1; the disease is myelodysplastic syndrome.