Nutritional modulation of epigenetic signatures of musculoskeletal ageing.

Aim: To measure biological age in normal and diseased human musculoskeletal tissues and to use population and cell culture systems to test the effect of nutrients on the epigenetic clock.
Objectives:
1) To analyse epigenetic age in upcoming Illumina 450k array data from an existing cohort of 100 people (age:40-60, BMI:25-40). Data will be correlated with nutrient metabolite, musculoskeletal biomarker (serum PINP, CTX, COMP, urinary CTX-II), musculoskeletal disease, exercise and food frequency questionnaire information10.
2) To measure intrinsic epigenetic age in normal and diseased human ligament, tendon, cartilage and bone using Illumina 850k arrays.
3) To treat cells isolated from these musculoskeletal tissues with micronutrients to modulate the epigenetic clock. B-series vitamins, choline, betaine, folate, vitamin C and polyphenols that may alter DNA methylation will be considered. Cells will be grown in
both 2D and 3D culture systemsand the epigenetic age measured after treatment.

Training in generating and analysing DNA methylation data using Illumina methylation arrays, will take place in Newcastle wit Dr Byun Training in the isolation of DNA and cells from musculoskeletal tissues will take place with Dr Laird in Liverpool. Dr Laird will introduce 3D cell culture systems for musculoskeletal cells and give guidance together with Prof Clegg on ethical amendment applications. We will also collaborate with Dr Reynard at Newcastle who has agreed to provide scripts for age regression methylation analysis and with Dr Peffers at Liverpool.
Cross-site supervisory meetings will take place every 1-2 months by Skype. The student will present their recent work for discussion and to obtain suggestions and help from each supervisor. The potential student would be part of the CIMA student cohort and will therefore know the other CIMA students and be aware of their projects. Supervisors will liaise with other supervisors for which the project may be relevant to share data, ideas and progress.