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.

Highlights

  • Received: 23 August 2021 Accepted: 19 October 2021 Published: 12 November 2021Citation: Carini G, Musazzi L, Bolzetta F, Cester A, Fiorentini C, Ieraci A, Maggi S, Popoli M, Veronese N and Barbon A (2021) The Potential Role of miRNAs in Cognitive Frailty

  • We explored the possible use of miRNAs as both potential biomarkers and molecular effectors of frailty and cognitive impairment

  • We discussed the evidence linking changes in circulating miRNAs expression with these clinical conditions, with the final aim of shedding light on miRNAs that might be associated with cognitive frailty

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Summary

INTRODUCTION

CLINICAL, CELLULAR, AND MOLECULAR MECHANISMS OF FRAILTY: THE POTENTIAL ROLE OF miRNAs. Frailty is generally considered as a geriatric syndrome, characterized by an excessive vulnerability to endogenous and exogenous stressors, due to a decrease in physiological reserves, leading to a high risk of developing adverse health outcomes (Clegg et al, 2013; Proietti and Cesari, 2020). Lifelong accumulation of molecular and cellular damages is believed as a key element of both physiological aging and frailty, the interplay among dysfunctions in the brain, endocrine system, immune system, and skeletal muscle functions is recognized as a main factor in the development of frailty (Figure 2; Clegg et al, 2013).

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