| Literature DB >> 27783938 |
Karla A Mark1, Kathleen J Dumas2, Dipa Bhaumik1, Birgit Schilling1, Sonnet Davis1, Tal Ronnen Oron1, Dylan J Sorensen1, Mark Lucanic1, Rachel B Brem1, Simon Melov1, Arvind Ramanathan1, Bradford W Gibson1, Gordon J Lithgow3.
Abstract
Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer's disease, Parkinson's disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1. Vitamin D3 (D3) induced expression of SKN-1 target genes but not canonical targets of XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.Entities:
Keywords: Alzheimer’s disease; Ceanorhabditis elegans; IRE-1; SKN-1; XBP-1; insoluble protein; lifespan. aging; protein aggregation; proteostasis; vitamin D
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Year: 2016 PMID： 27783938 PMCID： PMC5689451 DOI： 10.1016/j.celrep.2016.09.086
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423