Impact of Aging on Lipid Metabolism in Response to Traumatic Brain Injury

Traumatic brain injury (TBI) is a prominent health concern globally and is especially prevalent among young children and older adults. Despite the prevalence and impact of TBI, our understanding of the underlying pathophysiological mechanisms in repair and recovery remains incomplete. Aged individuals have poorer outcomes and longer recovery times compared to young. Young individuals have greater plasticity and capacity to remodel brain tissue post-injury, a process that requires high rates of energy production and membrane remodeling. Brain phospholipids are not only significantly impacted by TBI, but also susceptible to age-related changes. To determine the impact of age and time on lipid metabolism during injury and recovery, TBI was induced by cortical impact in 3-month-old and 18 months-old mice in the temporal lobe and ipsilateral cortex tissue was harvested at 1-, 3-, 7-, and 28-days post injury (dpi). Ipsilateral cortical RNA was isolated for gene expression analysis of lipid metabolizing genes. Untargeted and targeted lipidomics were used to analyze phospholipids (PL) and acylcarnitines, respectively. Injury gene markers increased during the first week after injury and returned to near baseline levels by one month. Nearly all lipid metabolizing genes were downregulated 1 dpi and subsequently upregulated in the following week. The aged animals demonstrated less fluctuation in gene expression profiles across the time course. Aged mice increased fatty acid activation genes while young mice repressed both fatty acid activation and deactivation genes. Aged mice had higher mono- and di- unsaturated phospholipids and lower saturated and highly polyunsaturated phospholipids during recovery. Arachidonic acid (AA)-containing PLs increased post TBI, whereas docosahexaenoic acid (DHA)-containing PLs steadily declined. Acylcarnitines, indicators of fatty acid oxidative flux, were increased in both young and aged cohorts following injury and restored to sham levels by day 28. Together, these data suggest that fatty acid oxidation and polyunsaturated fatty acid (PUFA) metabolism are essential for injury repair at any age, however, aging reduces the brain's ability to respond to TBI by these mechanisms. Therapies that target PUFA metabolism, specifically through DHA, may improve recovery in older adults. r01: DK125812 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.