Fig. 4

MAPK, JAK/STAT and TGF-β pathways regulate ageing and immunity. Multiple signalling cascades in addition to the IIS and TOR pathways contribute to ageing, longevity and immunity. Three MAPK pathways are conserved in worms, flies and mammals. The ERK-MAPK pathway is activated by growth and other factors through binding to receptors, including EGFR, and can further be triggered by the IIS pathway. Activity leads to transcription factors mainly promoting growth, cell division and differentiation of cells. In contrast, p38 and JNK MAPK pathways are classically considered to respond to stress including infections, while the JNK cascade is also mediated by Nf-κB signalling (Fig. 1). The multiple transcription factors downstream of p38 and JNK stimulate inflammation, immunity, longevity and other functions. JAK/STAT signalling is triggered by upd cytokines in D. melanogaster, and interferons, multiple cytokines and other factors in mammals. Upon receptor binding, the JAK/STAT signalling cascade leads to activation of STAT transcription factors, which are best known for fostering inflammation and immunity, particularly against viral infections. Notably, JAK/STAT in C. elegans only includes the two STAT transcription factors, sta-1 and sta-2, but does not share the same upstream factors as fruit flies and mammals. Finally, the branches of TGF-β pathways are activated by BMPs, activins and other factors. The signalling cascade regulates multiple transcription factors, leading to immunosuppression, anti-inflammatory responses and several other physiological effects. Notably, the pathways show various amounts of cross-regulation among each other but also with the IIS/TOR network and the Nf-κB cascade, and for simplicity, only well-known cross-talk is indicated. Gene names are given in the white boxes in the order of C. elegans, D. melanogaster and H. sapiens (overall, equal to M. musculus). Genes and factors concomitantly involved in lifespan, ageing, and immunity are marked in green and bold