Project Summary/Abstract By 2030, the majority of World Trade Center (WTC) rescue and recovery workers (responders) will be aged 65 and over and at risk for aging-related conditions and consequences. Although the WTC General Responder Cohort (WTC-GRC) is aging (median age is 59 in 2021), the WTC Health Program (WTCHP) does not routinely collect data on aging-related syndromes. In particular, frailty is a common geriatric syndrome characterized by increased vulnerability to adverse events including mortality, morbidity, disability and hospitalizations. Recently, our multidisciplinary research team has developed a WTC-specific frailty assessment tool (i.e., WTC Clinical Frailty Index/FI) based on clinically observable signs and symptoms of aging regularly examined within WTCHP surveillance. Our preliminary data indicate that approximately 30% of the WTC-GRC meets criteria for frailty as determined by WTC Clinical-FI, an association that increases with age, WTC exposure, and by occupation type (e.g., higher risk among construction worker). These findings underscore the urgent need for routine systematic assessments of structured aging-related indicators such as frailty in the WTC-GRC. Moreover, we began pilot work to prospectively assess physical measures (e.g., Frailty Phenotype) and consequences of frailty (e.g., functional impairment, falls) in WTC general responders who are followed at the Mount Sinai Clinical Center of Excellence (CCE) with an aim to improve the accuracy of the WTC Clinical-FI. These efforts have provided the necessary first step to more accurately measure frailty in WTC general responders. Thus, the overarching goals of this project are to further develop WTC Clinical-FI to study frailty progression and associated risk factors and clinical outcomes, and begin piloting frailty interventions in WTC general responders. Specially, we will determine frailty trajectories and risk factors associated with these distinct trajectories using the repository of WTC-GRC health monitoring data already collected at the Mount Sinai CCE (Aim 1); validate WTC Clinical-FI against Frailty Phenotype and determine its predictive validity for aging-related clinical outcomes such as functional decline and falls in a longitudinal cohort of general responders (Aim 2); and implement a pilot multicomponent intervention targeting modifiable risk factors of frailty such as inappropriate medication use in a subset of general responders (Aim 3). Identifying modifiable risk factors for frailty has the potential to impact the aging WTC responders of the entire WTCHP. Results of this study will be instrumental in improving the capacity of WTCHP to monitor and care for aging responders through partnership with Mount Sinai's nationally recognized Geriatrics and Palliative Care programs including the development of future widespread multifactorial preventive programs tailored to WTC responders to promote healthy aging.