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Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes including falls, incident disability, hospitalization, and mortality. It is characterized by multisystem dysregulations, leading to a loss of dynamic homeostasis, decreased physiologic reserve, and increased vulnerability to stressors. A large body of literature suggests several important multisystem pathophysiologic processes in the pathogenesis of the frailty syndrome, including chronic inflammation and immune activation, insulin resistance and those in musculoskeletal and endocrine systems. Currently, no effective pharmaceutical interventions have been developed for the prevention and treatment of the frailty syndrome. Conversely, epidemiological and intervention studies suggest that adequate nutrition and physical exercise might prevent or postpone the onset of frailty and related clinical manifestations.