Award Title: Does major trauma accelerate
 the ageing process and can it be alleviated by physical activity?
Funder: The Scar Free Foundation

Abstract: Major trauma survivors have a 5-year increased risk of death compared to the general population. These patients are also at increased risk of developing other age-related diseases such as dementia earlier than non-injured counterparts, suggesting that they may be ageing faster. Until recently there has been no reliable biomarker for a person’s biological versus their chronological age, but Horvath has reported a DNA methylation profile, termed the epigenetic clock, that showed a very strong association with chronological age, with deviations from this association indicative of the degree of biological ageing. There are also proteomic biomarkers being developed that give an indication of an individuals ageing trajectory and risk of future age-related disease, for example the Somascan proteomic platform. Furthermore, our own studies show that physical activity can help to reduce the ageing trajectory, benefitting several body systems.  
Aims and Hypothesis: We hypothesise that major trauma victims will show evidence of accelerated age-specific DNA methylation. In addition, that those subjects who have engaged in regular physical activity will show a lower impact of trauma on their biological age. 
Methods: The ADVANCE cohort of military trauma survivors, plus matched uninjured veterans represent an ideal cohort to test the hypothesis. They are all male and young thus reducing potential variance in data. In addition their thorough check-ups at Stanford Hall provide data for their level of involvement in physical activity/exercise. We will use stored blood samples (whole frozen EDTA blood, or blood spots), to measure DNA methylation using the Illumina Human Methylation EPIC array and calculate the DNA methylation age of injured and uninjured veterans. Serum will also be analysed for protein markers of accelerated ageing, using the Somascan platform. Data on physical fitness (6 min walk test, Chester step count, military multistage fitness test) will be used to divide the cohort in to those in the top quartile and those in the lower quartile in order to assess potential impact of physical activity on DNA methylation age.
We aim to gain sufficient pilot data to apply for further funding from funders such as the MRC or Wellcome Trust by analysing 100 military and 50 healthy subject samples.

Lay Abstract: Until recently there has been no way of measuring how fast someone was ageing but now a test is available that uses blood cells to determine how biologically old a person is. Survivors of a major injury, such as that experienced in conflict by the military or a road traffic accident in civilian life, have shortened lifespans. They also develop age-related diseases such as heart disease, diabetes and dementia earlier than non-injured adults. This suggests that because of their injuries they may be ageing faster. In this study we aim to measure biological age in a large group (150) of military veterans from the Afghanistan conflict, assessing 100 who were injured and 50 who were not.

Research Activity Codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health Categories: GENERIC HEALTH RELEVANCE;INJURIES AND ACCIDENTS