Working with collaborators in Kings College London, University of Bristol, and MRC LHA, we aim to delineate the developmental processes (genetic, epigenetic, metabolomic and proteomic) that influence longevity and musculoskeletal ageing; and to investigate the impact of objectively measured physical activity in retarding the involutional loss of bone strength, muscle mass and function.

Using a systems biology approach, through an EU Framework 7 Programme bringing together two birth cohorts with extensive perinatal information and offspring now in their seventh decade of life (HCS and the Northern Finnish Birth Cohort) as well as the largest UK twin collection (Twins UK), we are investigating links between birthweight and (osteoporosis, sarcopenia, osteoarthritis, and all-cause mortality). This is complemented by the MRC-ESRC LLHA- funded VIBE study, bringing together Hertfordshire Cohort and NSHD to explore the objectively measured physical activity and impact characteristics on musculoskeletal health. The addition of a SCANCO Xtreme CT high-resolution peripheral quantitative CT scanner has greatly enriched the phenotypic detail available for outcome assessment.

These studies will provide much-needed mechanistic information on the genetic, epigenetic and metabolic correlates of both intrauterine growth and adult musculoskeletal disease. They hold the prospect of discovering novel epigenetic biomarkers which can be replicated in our mother-offspring cohorts and future intervention studies. Finally, they will lead to greater understanding of the role of physical activity, in particular impact loading, in the natural history of musculoskeletal ageing.