Recently, some studies have demonstrated that CR or IF can moderate the harmful off-target effects of allergies and autoimmunity and protect against cancer and pathogens through optimization of immune responses.175–179 In C. elegans, CR or reduced insulin/IGF-1 signalling has been found to downregulate p38-ATF7 signalling to a basal level in the innate immunity pathway, which contributes to the extension of lifespan.178 In mice and humans, CR ameliorates ageing-associated alterations in transcriptional regulatory networks, expression of key genes and the composition of cell types. Here, INS is linked to cancer.