The psychiatric aftermath of severe traumatic stress, including Post-Traumatic-Stress Disorder (PTSD), is well recognized; however, less attention has been given to the growing evidence that Veterans with PTSD experience biological and cognitive deterioration. Specifically, PTSD is associated with an earlier occurrence of age-associated medical illnesses, higher risk of cognitive impairment and dementia, and higher mortality rates compared to those without PTSD. Whether this deterioration is best characterized as premature or accelerated aging is presently unclear but could have implications for future interventions and their timing. In addition, the mechanism(s) underlying the comorbidity, cognitive deficits, and mortality associated with PTSD are presently unknown. However, given the association of inflammation with aging and health and with PTSD, pro- inflammatory markers appear a viable candidate to identify the underlying mechanisms. Through a Multi- Cohort Longitudinal Design we will compare 80 Veterans with PTSD to 80 normative comparison Veterans without PTSD across a critical period of the adult life span (26-65 years), and examine within-person changes over a 2.5 year follow-up period on biological markers of aging (leucocyte telomere length and allostatic load), cognitive aging (neurocognitive performance), as well as physical comorbidity. We will also examine several key pro-inflammatory biomarkers (HS-CRP, IL-1β IL-6, and TNFα). This will enable us to confirm whether the systemic and cognitive deterioration associated with PTSD is best characterized as accelerated versus premature aging, and the potential role of inflammatory processes in that deterioration. We will also conduct exploratory analyses of alternative models of factors that could mediate the association of PTSD and/or its severity to biological aging. These include gender, ethnicity, socioeconomic status, education level, exposure to psychological trauma, combat exposure, TBI (number of brain traumas and severity), smoking and substance abuse, sleep disturbance, and sedentary lifestyle. If PTSD is associated with accelerated aging, this disorder may require re-conceptualization and treatment as a chronic systemic disorder rather than a purely neuropsychiatric condition. Moreover, if the neurobiologic mechanisms of the cognitive and biological deterioration can be identified, new treatment targets may emerge to supplement those for the psychiatric aspects of the condition. This information could have a profound effect in guiding appropriate and effective treatment for Veterans with PTSD to improve physical health, longevity, and quality of life.