Accelerated epigenetic ageing after burn injury

Individuals who suffer a major burn injury are at higher risk of developing a range of age-associated diseases prematurely leading to an increase in mortality in adult and juvenile burn injury survivors. One possible explanation is that injury is accelerating the biological ageing process. To test this hypothesis, we analysed DNA methylation in peripheral blood mononuclear cells from adult burn-injured patients (> 5%TBSA) upon admission to hospital and 6 months later, to calculate an epigenetic clock value which can be used to determine biological age. Fifty-three burn-injured participants (mean age 45.43 years, 49 male, mean TBSA 37.65%) were recruited at admission and 34 again 6 months post injury (mean age 40.4 years, 34 male, mean TBSA 30.91%). Twenty-nine healthy controls (mean age 43.69 years, 24 male) were also recruited. Epigenetic age acceleration at admission by PhenoAge was + 7.2 years (P = 8.31e-5) but by month 6 was not significantly different from healthy controls. PCGrimAge acceleration was + 9.23 years at admission (P = 5.79e-11) and remained 4.18 years higher than in controls by month 6 (P = 2.64e-6). At admission, the burn-injured participants had a Dunedin PACE of ageing score 31.65% higher than the control group (P = 2.14e-12), the equivalent of + 115 days per year of biological ageing. Six months post injury the Dunedin PACE of ageing remained significantly higher (+ 11.36%, 41 days/year) than in the control group (P = 3.99e-5). No differences were seen using the Horvath and Hannum clocks. Enrichment analysis revealed that key pathways enriched with burn injury related to immune function, activation, and inflammation. The results reveal that epigenetic age, specifically the PACE of ageing and PCGrimAge, was accelerated in burn-injured adults at admission, with some return towards control values by 6 months. That these two clocks are built upon morbidity outcomes suggests that the injury is invoking a biological response that increases the risk of disease. Burn injury in adults induces epigenetic changes suggestive of an acceleration of the ageing process, which may contribute to the increased morbidity and mortality in these patients.