When considering this custodial action of vitamin D, it is
important to include the activity of the nuclear factor-erythroid-2-
related factor 2 (Nrf2) and Klotho, because their expression is
regulated by Vitamin D (Fig. 2). Both Klotho, which has been
implicated in ageing and Nrf2 are included in the hypothesis because
they also function to maintain the stability of cell signalling pathways. The vitamin D signalling stability hypothesis proposes that
Vitamin D, working in conjunction with Klotho and Nrf2, creates an
extensive regulatory network that acts as a custodian to ensure the
normal function of both the ROS and Ca2þ signalling pathways.