Project 459101

Severe burns account for an estimated 330,000 deaths per year worldwide- ranking fourth in incidence among all forms of trauma. While modern burn care has markedly improved survival for pediatric and adult patients, this is sadly not the case for one population: the elderly. Despite being the fastest-growing demographic in North America, elderly burn patients still have the highest mortality and morbidity rates. Recently, we discovered that progressive aging induces several structural and functional defects which impair the capacity of older trauma patients to adequately respond to stress, consequently leading to poor outcomes. We further found that this 'failure-to-respond' is associated with completely depleted NAD levels and dysfunctional mitochondria. Interestingly, the widely used hypoglycemic drug, metformin, has been found to protect against these age-related metabolic disturbances and therefore seems ideally suited to effectively treat the pathophysiologic response to burns in the elderly. Additionally, metformin is a well-characterized agent and has little side-effects, making it an even more attractive treatment. Thus, the purpose of this prospective, single-centre translational study is to determine whether metformin can improve survival outcomes of elderly burn patients. Utilizing a mix of basic and clinical techniques, I will answer fundamental questions and mechanisms by which metformin exerts its benefits in the context of burns and aging. Importantly, results generated by this study will have direct clinical implications as they can be applied to improve the morbidity and quality of life of elderly burned patients. As age is a major risk factor for most chronic diseases, these findings can also be translated to fields beyond burn trauma and potentially change the face of care for many patients worldwide. Our strategies to transform care and outcomes for the elderly are visionary and necessary to reduce the health care burden in the imminent future.