Burn Injuries Accelerate Biological Aging and Increase the Epigenetically Inferred Risk of Mortality and Frailty.

Abstract

Biological aging is closely associated with heightened disease risk, frailty, and mortality. Interestingly, physical traumas, such as burn injuries, exhibit physiological effects that resemble those of aging. However, the impact of burn injuries on biological aging remains underexplored, creating a gap in the literature that could inform better prognosis and outcomes. We conducted a prospective cohort study to investigate the effects of burn injuries on various epigenetic clocks, including HorvathAge, GrimAge, PhenoAge, and DunedinPoAm, using whole blood. The study included 59 burn patients and 25 healthy controls and was validated using a murine model of thermal injury. Our study demonstrates that burn injuries accelerate biological aging and the rate of aging, with these effects persisting for up to 28 days post-injury. The extent of biological aging was positively correlated with burn size, with severe burns resulting in an acceleration of 13-14 years in biological age as measured by GrimAge and PhenoAge-double the acceleration observed with chronic long-term smoking. This acceleration occurred irrespective of age or sex, though older patients were the most vulnerable to the aging effects of burn injuries. The role of burns as an accelerator of aging was further confirmed in mice, which exhibited the equivalent of 3-6 human years of accelerated aging (8 mouse months, or 7 human days) after the injury, reinforcing the chronic nature of the effect. Additionally, burn injuries increased epigenetically inferred risks of frailty and mortality in humans, highlighting their long-term and enduring consequences. Collectively, our findings identify burn injuries as the most significant and chronic accelerant of biological aging reported to date. To our knowledge, this study is one of the first to link burn injuries-or any form of physical trauma-to accelerated cellular and biological aging.