Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1.
Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1.
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DOI：
10.1016/j.celrep.2016.09.086
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发表时间：
2016-10-25
期刊：
影响因子：
8.8
通讯作者：
Lithgow GJ
中科院分区：
文献类型：
--
作者：
Mark KA;Dumas KJ;Bhaumik D;Schilling B;Davis S;Oron TR;Sorensen DJ;Lucanic M;Brem RB;Melov S;Ramanathan A;Gibson BW;Lithgow GJ
维生素D有多种作用，包括调节骨骼和钙的体内平衡。缺乏25-羟基维生素D（维生素D的主要循环形式）与老年相关慢性疾病（包括阿尔茨海默病、帕金森病、认知障碍和癌症）的风险增加有关。在这项研究中，我们利用秀丽隐杆线虫来研究维生素D影响衰老的机制。我们发现维生素d3诱导的寿命延长需要应激反应途径基因SKN-1、IRE-1和XBP-1。维生素D3 （D3）诱导SKN-1靶基因的表达，但不能诱导IRE-1/XBP-1的典型靶基因表达。D3抑制了一种重要的衰老分子病理，即广泛的蛋白质不溶性，并防止了人类β-淀粉样蛋白引起的毒性。我们观察到D3可以改善蛋白质稳态并减缓衰老，这突出了维持适当的维生素D血清水平的重要性，并可能解释为什么如此广泛的人类年龄相关疾病与维生素D缺乏有关。维持蛋白质稳态对细胞健康至关重要，并对生物体的寿命有重要贡献。Mark等人证明，补充维生素D可以促进线虫（秀丽隐杆线虫）的蛋白质稳态，减缓衰老。这些发现确定了维生素D影响衰老的机制。
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 IRE-1/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. Maintenance of protein homeostasis is crucial to cellular health, and contributes significantly to the lifespan of the organism. Mark et al. demonstrate that vitamin D supplementation promotes protein homeostasis and slows aging in the nematode, C. elegans. These findings identify a mechanism by which Vitamin D influences aging.
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