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

Lead Research Organisation: University of Manchester
Department Name: Earth Atmospheric and Env Sciences

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011208/1 01/10/2015 31/03/2024
1917097 Studentship BB/M011208/1 01/10/2017 30/09/2021
 
Title Clinical study samples 
Description REC approved clinical study allowed for collection of blood samples and skin biopsies for further analytical chemistry analyses 
Type Of Material Biological samples 
Year Produced 2018 
Provided To Others? Yes  
Impact Clinical study protocol 
URL https://www.isrctn.com/ISRCTN72674753?q=&filters=condition:vitamin%20d&sort=&offset=11&totalResults=...
 
Description Collaboration with Prof William Fraser's lab from the University of East Anglia, Norwich 
Organisation University of East Anglia
Department School of Medicine UEA
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing a novel Mass Spectrometry assay in Satellite UEA Lab in Runcorn. Currently working on assay validation, hoping for work to be finalised in the next few months.
Collaborator Contribution Provided expertise and lab space in Satellite UEA Lab in Runcorn Also a few day unofficial training in UEA, Norwich regarding Vitamin D derivatives in blood & High-performance liquid chromatography Mass Spectrometry methods.
Impact - Development of a novel HPLC-MS assay (analytical chemistry)
Start Year 2017
 
Description Help with organisation of BBSRC Doctoral Training Partnerships Conference 2018, 20th June 2018, Manchester 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Help with organisation of BBSRC Doctoral Training Partnerships Conference 2018, 20th June 2018, Manchester
Arranging Key Note speaker to give a presentation at the conference
Year(s) Of Engagement Activity 2018