Project Summary/Abstract
Burn care in older adult patients has been extremely challenging. Not only do elderly burn patients have an
increased susceptibility to burns, but more importantly, they have a substantially increased morbidity and
mortality compared to adults. The cause and underlying mechanisms for these adverse outcomes are
essentially unknown. We recently conducted several studies in older adult burn patients and aged mice to
understand the pathophysiology after a burn. We found that older adult burn patients are hypo-inflammatory
and hypometabolic. It, therefore, appears that elderly burn patients cannot initiate ubiquitous life-saving
responses to burn. As we have recently shown that the adipose tissue is a central mediator for post-burn
immune-metabolic responses, we investigated the response of the adipose tissue after a burn in older adult
burn patients and aged mice. We found that older adult burn patients have an absence of the adipose tissue
adaptive response, namely the browning of the adipose tissue and its ensuing immune-metabolic responses.
Looking at a more molecular level, we found that older adult burn patients have profound mitochondrial
dysfunction and depleted NAD levels. These findings indicate that the structure and the immune-metabolic
function of the adipose tissue are substantially different in older adults compared to adults after a burn leading
us to hypothesize that the adipose tissue is a central mediator in the post-burn response of older adults. To
enable mechanistic studies, we conducted several experiments to determine if the previously mentioned
phenomena can be recapitulated in aged mice. We found that aged mice underwent the same functional and
structural changes of the adipose tissue and very similar immune-metabolic responses compared to older adult
burn patients. Therefore, we concluded that aged mice could be used for our proposed studies, allowing
translation from aged mice to older adult patients. Our overarching hypothesis is that the adipose tissue and its
ensuing immune-metabolic responses are central to survival in burn patients. The dysfunctional adipose tissue
found in older adult burn patients is one of the key mechanisms resulting in poor outcomes in this patient
population.