Frailty in Older Adults: Pathogenesis, Treatment and Prevention

Abstract Purpose of Review Frailty is a geriatric syndrome of loss of reserves, characterized by multisystem dysregulations, limited capacity to maintain homeostasis, and increased vulnerability. This review is focused on the current knowledge on the main pathogenic mechanisms leading to frailty and on evidence-based improvements in its prevention and treatment. Recent findings The physiological processes altered in frail patients can be grouped into three dimensions. At the cellular level, frailty is related to increased oxidative stress, deficiencies in cellular repair capacity and subsequent accumulation of genetic damage, and epigenetic modifications. At the system level, the physiological dysregulation involves multi-organ systems, including primarily the immune system, endocrine system and energy metabolism. At the organism level, these dysregulations become physically evident as the clinical signs of frailty, including loss of muscle mass and neurocognitive impairment. Among a wide variety of strategies, current evidence supports multicomponent physical exercise, nutrition (to ensure calorie and protein intake), control of vitamin D, and reduction of polypharmacy as effective approaches for prevention and treatment of frailty. Ideally, they can be applied as multimodal and personalised interventions. Summary A deeper knowledge on the pathophysiological mechanisms involved in frailty development is useful to guide targeted interventions to preserving the functional and cognitive reserves of older adults, maintaining their capacity for self-care, and preventing negative health outcomes. Apart from the evidence-supported interventions to prevent or treat frailty, many others are currently under investigation.