Research Paper Volume 2, Issue 9 pp 567—581

Klotho interferes with a novel FGF-signalling pathway and insulin/Igf-like signalling to improve longevity and stress resistance in Caenorhabditis elegans

Figure 6. In adult worms the FGFR EGL-15(5A) targeted for activation by the Klotho KL1 isoform can allow EGL-17 ligand binding. Under physiological conditions, the Klotho/EGL-15/EGL-17 complex constitutively represses the DAF-2 (Insulin/Igf-like) receptors by a still unknown pathway. Such complexes may induce DAF-16 (FOXO) de-repression and subsequent overexpression of longevity factors, such as antioxidant enzymes. When worms have to cope with a potent stress, the Klotho/EGL-15/EGL-17 complex may directly activate DAF-16 by a DAF-2-independent pathway (dashed line). Such activation mechanism remains to be elucidated.