title: 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) landscape that initiates amyloid formation, which then elevates the resting level of Ca(2+) to drive the memory loss that progresses to neuronal cell death and dementia.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.
authors.affiliation: Babraham Institute, Babraham, Cambridge CB22 3AT, UK michael.berridge@babraham.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Berridge
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006331:Heart Diseases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D014807:Vitamin D; D002118:Calcium
keywords: Alzheimer's disease; calcium; cardiac disease; inositol trisphosphate; klotho; vitamin D