Involvement of plasma miRNAs, muscle miRNAs and mitochondrial miRNAs in the pathophysiology of frailty

Frailty is a geriatric syndrome that leads not only to the loss of physical functions, but also to a generalized decline of the organism and a high risk of disability and dependency. Frailty's detection and management represent important goals for current gerontology. The advance in its rapid diagnosis could play a relevant role in taking measures to reduce the negative consequences it exerts on the body and to take preventive measures. microRNAs are the one of multiple epigenetic biomarkers that reflect functional changes in aged subject. In this review we analyze microRNAs as molecules involved in the control of the pathways leading to the development of frailty. miRNAs can be present in different body fluids, including plasma/serum and saliva, can be associated with organelles like the mitochondria, and can be expressed in tissues. Based on the multifactorial physiopathology of frailty, we analyzed here the microRNAs linked to “inflammaging” (inflamma-miRs), to musculoskeletal health (myomiRs), and microRNAs that can directly or indirectly affect the mitochondria (mitomiRs). Subsequently, we analyze those microRNAs that can be modified by physical exercise. In this review we will analyze the latest experimental studies carried out in animals, cell cultures, and human samples, with the aim to identify gaps in the research and in order to try to dazzle the information about the pathways regulated by each miRNA. Multiple studies revised here suggest that several miRs can be considered as possible markers of frailty, including miR-1, miR-21, miR-34a, miR-146a, miR-185, and miR-206, miR-223, among others. Normalization of miRNAs data and standardization of the protocols used for their measurement to avoid confounding variables influencing the results, are important to use miRNAs as disease biomarkers. •Frailty is a predictor of all causes of mortality in aged population.•miRs and epigenetic control of aging and frailty•myomiRs and mitomiRs in muscle- and mitochondria-associated impairment in frailty•Circulating miRs as multisystemic biomarkers of frailty