Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

Abstract

Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca2+ and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca2+ and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer’s disease (AD). In cardiac cells, this deficiency alters the Ca2+ transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca2+ landscape that initiates amyloid formation, which then elevates the resting level of Ca2+ to drive the memory loss that progresses to neuronal cell death and dementia. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’.