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.

Keywords: MCI (mild cognitive impairment); biomarkers; cognitive frailty; cognitive impairment; frailty; miRNA–microRNA.

FIGURE 1

miRNAs in frailty and cognitive deficits. miRNAs play a major role in RNA silencing and post-transcriptional regulation of gene expression. miRNAs target hundreds of transcripts to regulate various biological pathways and processes, repressing translation or inducing mRNA degradation of target transcripts through sequence-specific binding. miRNAs are key modulators of almost all physiological processes and, consequently, miRNA dysregulation is seen in a multiplicity of diseases, including frailty and cognitive deficits.

FIGURE 2

Common mechanisms underlying frailty and cognitive deficits. The high majority of mechanisms known to be involved in frailty were also implicated in cognitive diseases, including oxidative stress, inflammaging, mitochondrial dysfunction, cellular senescence, neuroendocrine dysfunctions, and impaired neuronal plasticity.