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

众所周知，被称为维生素D的开环类固醇激素对肌肉骨骼健康至关重要，但现在很明显，许多细胞都有维生素D及其代谢物的受体，维生素D与一系列其他健康益处有关，导致人们广泛呼吁改善人口的维生素D状况。由于现代饮食中维生素D含量很少，主要来源是暴露在阳光下，当紫外线辐射作用于皮肤细胞中的前体7-脱氢胆固醇（7 DHC）时。前体维生素D的水平被认为会随着年龄的增长而下降，但目前尚不清楚老年皮肤中的维生素D合成是否受到7 DHC限制，或者是否缺乏阳光照射导致老年人对维生素D水平低的担忧。了解老龄化人口中维生素D合成的限制将有助于有针对性地建议在生命阶段保持适当的状态，因为保持强大的肌肉骨骼系统至关重要，与维生素D相关的其他益处也是如此。通过前体7-脱氢胆固醇（7 DHC）的可用性及其UV转化。该项目将涉及一项比较研究，涉及两个年龄组的人类志愿者，年轻人和老年人。皮肤（前体7 DHC）和血液（维生素D和25-羟基维生素D，维生素D状态的测量）将在受控剂量的模拟日光之前和之后采集。串联质谱法是用于分析所有样本的技术，在项目期间，将改进从组织中制备样本的提取程序，以提高对小皮肤活检样本分析的灵敏度。结果将与以前和正在进行的研究相比较，这些研究评估了不同年龄的几个人群全年的维生素D状况。它将确定老年人皮肤中的维生素D合成是否受到7 DHC限制，在这种情况下，必须考虑替代干预措施，以实现良好维生素D状况的所有健康益处，或者生活方式的微小变化是否可能通过暴露于紫外线辐射导致这种改善，正如我们以前的工作所评估的那样，基于详细的英国气候学。该项目支持技术发展，加强多学科研究的技能基础，体内技能。组织样本中维生素D相关分子的分析正在开发中，组织提取技术将进一步完善（提高分析对pmol的灵敏度），并在本项目期间得到证明。该项目有三个学科链，物理/辐射，皮肤病学/人类志愿者和实验室分析，为学生提供了一系列互补的技能，词汇和理解，以在学科之间进行翻译，以及将它们联合收割机结合起来的愿景。

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.