Objective:Comprehensive characterization of potential frailty determinants, including sociodemographic, clinical, dietary, psychological, cognitive and systemic inflammation parameters. Methods:A rural cohort of 186 subjects aged 60-89 years recruited from a community-based study in Crete, Greece (the Cretan Aging Cohort). Frailty was assessed with the Simple "Frail" Questionnaire Screening Tool. Results:Univariate analyses revealed significant (a) positive associations (p<0.01) between frailty and age, widowhood, Geriatric Depression Scale (GDS) score, waist circumference, polypharmacy, IL-6 and (b) negative associations between frailty and frequency of contact with friends, Mini Mental State Examination (MMSE), and adherence to the Mediterranean diet. Multivariate analyses revealed a significant independent contribution of the following variables to frailty: age (B=0.035, p<0.001), GDS score (B=0.041, p=0.034), polypharmacy (B=0.568, p<0.001), waist circumference (B=0.015, p=0,006), plasma IL-6 levels (B=0.189, p=0.004), and adherence to the Mediterranean diet (B=-0.036, p=0.015). Conclusion:Older age, depression symptoms, polypharmacy, waist circumference, poor adherence to Mediterranean diet and IL-6 plasma levels are associated with increased frailty.