INS and major depressive disorder: The function of klotho is complex and multifaceted, with known roles in regulating insulin,4 Wnt,13 fibroblast growth factor,14 nuclear factor kappa B,22, 51 tumor necrosis factor-α22, 52 and N-methyl-D-aspartate receptor signaling.12 Importantly, each one of these pathways, which may be dependent or independent of the aging process, can be linked directly or indirectly to stress or depression.