Exploring skin-age limits on the production of vitamin D in vivo

众所周知，被称为维生素D的类固醇激素对肌肉骨骼健康是必不可少的，但现在很明显，许多细胞都有维生素D及其代谢物的受体，这种维生素与一系列其他健康益处有关，导致人们普遍呼吁改善人群的维生素D状况。由于现代饮食中维生素D含量一般很少，主要来源是暴露在阳光下，紫外线辐射作用于皮肤细胞中的前体7-脱氢胆固醇(7DHC)。据了解，前体维生素D的水平会随着年龄的增长而下降，但尚不清楚老年皮肤中维生素D的合成是否受到7DHC的限制，或者是否缺乏阳光暴露导致人们对老年人维生素D水平低下的担忧。了解老龄化人口中维生素D合成的限制，将使人们能够有针对性地建议在生命阶段保持足够的状态，因为保持强大的肌肉骨骼系统至关重要，与维生素D相关的其他好处也是如此。该项目的目的是在细胞水平上确定，通过前体7-脱氢胆固醇(7DHC)的可获得性及其紫外线转换，在阳光下皮肤合成维生素D的年龄相关能力。该项目将涉及两个年龄段的人类志愿者的比较研究，其中包括年轻人和老年人。皮肤(前体7DHC)和血液(维生素D和25-羟基维生素D，维生素D状态的衡量标准)将在控制剂量的模拟阳光之前和之后进行采集。串联质谱仪是用于分析所有样本的技术，从组织中制备样本的提取程序将在项目期间进行改进，以提高对小样本皮肤活检样本的分析的灵敏度。结果将与之前和正在进行的评估几个不同年龄群体的维生素D状况的研究相对照。它将确定老年人皮肤中维生素D的合成是否受到7DHC的限制，在这种情况下，必须考虑替代干预措施，以实现良好的维生素D状态对健康的所有好处，或者生活方式的微小变化是否可以通过暴露在紫外线辐射中而导致这种改善，正如我们之前基于英国气候的详细评估所评估的那样。该项目支持技术开发，并加强多学科研究和体内技能的技能基础。对组织样本中维生素D相关分子的分析正在开发中，从组织中提取的技术将进一步改进(提高分析对PMOL的敏感性)，并在该项目中进行演示。该项目有三个学科分支，物理/辐射，皮肤病/人类志愿者，以及实验室分析，为学生提供一系列互补技能，在各学科之间进行翻译的词汇和理解，以及将它们结合在一起的愿景。

It is well known that the secosteroid hormone called vitamin D is essential for musculoskeletal health, but it is now apparent that many cells have receptors for vitamin D and its metabolites, and the vitamin has been associated with a range of other health benefits, leading to widespread calls for the vitamin D status of the population to be improved. Since modern diets generally contain little vitamin D the main source is exposure to sunlight, when UV radiation acts on the precursor 7-dehydrocholesterol (7DHC) in skin cells. The levels of precursor vitamin D are understood to decline with age, but it is not clear whether vitamin D synthesis in aged skin is 7DHC limited, or whether it is lack of sun exposure that leads to concern over low vitamin D status in the older population. Understanding the limits to vitamin D synthesis in an aging population will enable targeted advice on maintaining an adequate status at a life stage when retaining a strong musculoskeletal system is vital, as are the other benefits associated with vitamin D.The aim of the project is to identify, at a cellular level, the age-related ability to synthesise vitamin D in the skin on exposure to sunlight, through availability of the precursor 7-dehydrocholesterol (7DHC) and its UV-conversion. The project will involve a comparative study involving human volunteers in 2 age groups, young and aged adults. Skin (precursor 7DHC) and blood (vitamin D and 25-hydroxyvitamin D, the measure of vitamin D status) will be taken before and after controlled doses of simulated sunlight. Tandem mass spectrometry is the technique to be used for analysing all samples and the extraction procedures to prepare samples from tissue will be refined during the project to enable increased sensitivity from the analysis for the small skin biopsy samples.The results will be set in context against previous and on-going studies that have assessed the year-round vitamin D status in several population groups of different ages. It will identify whether vitamin D synthesis in the skin of the elderly is 7DHC limited, in which case alternative interventions must be considered in achieving all the health benefits of a good vitamin D status, or whether small changes in lifestyle might lead to such improvements through exposure to UV radiation, as assessed in our previous work based on a detailed UK climatology.This project supports technological development and strengthens the skills base in multidisciplinary research and in vivo skills. The analysis of vitamin D related molecules from tissue samples is under development and extraction techniques from tissue will be further refined (increasing sensitivity of analysis to pmols) and demonstrated during this project. The project has three discipline strands, physics/radiation, dermatology/human volunteers, and laboratory analysis, providing the student with a range of complementary skills, the vocabulary and understanding to translate between the disciplines, and the vision to combine them.