Molecular mechanisms of age-related vulnerability to traumatic brain injury.

Aging is associated with increased vulnerability to a wide variety of diseases and conditions, including traumatic brain injury (TBI). While advanced age is a known predictor of poorer outcomes following TBI, the molecular mechanisms underlying this susceptibility haven't been completely characterized. This review discusses some of the primary pathways and physiological changes that are affected by aging and how they influence the post-TBI recovery in both experimental and clinical settings. Some of the age-related alterations implicated in geriatric TBI include loss of white matter, compromised blood-brain-barrier integrity, aggravated oxidative stress, mitochondrial dysfunction, higher cell death and synapse loss, increased and more prolonged neuroinflammation, compromised neural repair mechanisms, dysregulated proteasomal degradation leading to misfolded protein aggregation, and systemic changes such as peripheral organ dysfunction. This review further focuses on how the underlying molecular mechanisms involved in these changes influence long-term functional and behavioral outcomes after TBI. Lastly, some of the current and potential therapeutic interventions for geriatric TBI have also been discussed.