The Potential Role of miRNAs in Cognitive Frailty

Abstract

Frailty is an aging related condition, which has been defined as a state of enhanced vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Cognitive impairment is also frequent in older people, often accompanying frailty. Age is the main independent risk factor for both frailty and cognitive impairment, and compelling evidence suggests that similar age-associated mechanisms could underlie both clinical conditions. Accordingly, it has been suggested that frailty and cognitive impairment share common pathways, and some authors proposed “cognitive frailty” as a single complex phenotype. Nevertheless, so far, no clear common underlying pathways have been discovered for both conditions. microRNAs (miRNAs) have emerged as key fine-tuning regulators in most physiological processes, as well as pathological conditions. Importantly, miRNAs have been proposed as both peripheral biomarkers and potential molecular factors involved in physiological and pathological aging. In this review, we discuss the evidence linking changes of selected miRNAs expression with frailty and cognitive impairment. Overall, miR-92a-5p and miR-532-5p, as well as other miRNAs implicated in pathological aging, should be investigated as potential biomarkers (and putative molecular effectors) of cognitive frailty.

Functional role of miR-34a in diabetes and frailty

“…Many miRNAs have been associated to mitochondrial dysfunction, inflammation, and oxidative stress and their concentration may vary in physiological conditions ( Zhang et al, 2014 ; Hathaway et al, 2018 ; Wei et al, 2018 ; Rusanova et al, 2019 ; Song et al, 2019 ; Gambardella et al, Forthcoming 2022 ). Interestingly, several investigators evidenced the potential roles of microRNAs (miRNAs) in the pathogenesis of frailty ( Rusanova et al, 2019 ; Carini et al, 2021 ; Lee et al, 2021 ; Carini et al, 2022 ; Dowling et al, 2022 ).…”

Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes

“…Nevertheless, there are limited reports investigating the functional role of potential biomarkers to monitor the effects of SGLT2 inhibitors. In this sense, miRs have been widely used as biomarkers; however, limited data are available on the miR profile in frailty (Ipson et al, 2018;Carini et al, 2021). Besides, there are no studies investigating miRs in terms of endothelial dysfunction in HFpEF or frailty.…”

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

“…A study of network biology, by analyzing the interactome of frailty-related genes, prioritized 10 miRNA markers indirectly associated with frailty through the association of their targets [ 66 ]. To date, only three studies directly evaluated changes in blood plasma miRNAs in frail/non frail subjects [ 67 , 68 , 69 ]. Rusanova measured levels of the inflammation-related miRNAs, miR-21, miR-146a, miR-223, and those of miR-483, associated with the control of melatonin synthesis, reporting an association between the expression of miR-21 with the presence of frailty [ 67 ].…”