Biomarkers of Frailty: miRNAs as Common Signatures of Impairment in Cognitive and Physical Domains

SIMPLE SUMMARY: A growing number of studies have focused their attention on the potential role of microRNAs (miRNA) as biomarkers for several diseases. However, very few evaluated the role of miRNAs in the aetiogenesis of frailty, a multidimensional geriatric syndrome, characterized by an individual and dynamic state of impairments in one or more domains, such as physical, cognitive, psychological, and social. In this review, we first provided an overview on the different frailty domains, current assessment tools and plasma/blood biomarkers. Then, we collected the evidence linking changes of miRNAs expression to impairment of frailty in physical and cognitive domains, with the ultimate aim of finding those that are common. In silico analyses prioritized ten top-ranked miRNAs and their targets, the three most significant regulating processes involved in inflammation and energy homeostasis pathway. Such miRNAs, through the integration with existing markers, may be useful for an early and accurate diagnosis of frailty in the elderly population. ABSTRACT: The past years have seen an increasing concern about frailty, owing to the growing number of elderly people and the major impact of this syndrome on health and social care. The identification of frail people passes through the use of different tests and biomarkers, whose concerted analysis helps to stratify the populations of patients according to their risk profile. However, their efficiency in prognosis and their capability to reflect the multisystemic impairment of frailty is discussed. Recent works propose the use of miRNAs as biological hallmarks of physiological impairment in different organismal districts. Changes in miRNAs expression have been described in biological processes associated with phenotypic outcomes of frailty, opening intriguing possibilities for their use as biomarkers of fragility. Here, with the aim of finding reliable biomarkers of frailty, while considering its complex nature, we revised the current literature on the field, for uncovering miRNAs shared across physical and cognitive frailty domains. By applying in silico analyses, we retrieved the top-ranked shared miRNAs and their targets, finally prioritizing the most significant ones. From this analysis, ten miRNAs emerged which converge into two main biological processes: inflammation and energy homeostasis. Such markers, if validated, may offer promising capabilities for early diagnosis of frailty in the elderly population.