Evaluation of serum miRNAs expression in frail and robust subjects undergoing multicomponent exercise protocol (VIVIFRAIL)

Abstract

Background Frailty, defined as physical performance impairment, is a common condition in older adults and can anticipate the development of sarcopenia, a geriatric syndrome characterized by loss of muscle strength and mass. microRNAs (miRNAs) are short molecules of RNA endowed with the ability to modulate gene expression; miRNAs are present in serum and are considered potential biomarkers for several diseases. Serum concentration of miR-451a, miR-93-5p, miR-155-5p, miR-421-3p, miR-425-5p, miR-495-3p and miR-744-5p was recently shown to be altered in sarcopenic patients. Methods We verified if a particular miRNAs pattern could be detected in frailty as well by analyzing these molecules in 50 frail and 136 robust subjects. Additionally, a subgroup of these subjects (15 frail and 30 robust) underwent a 12-week program based on a multicomponent exercise protocol (VIVIFRAIL) consisting of resistance training, gait retraining, and balance training. After the program, serum miRNAs concentration was measured again, to verify whether the physical activity had an effect on their concentration. Moreover, clinical characteristics and indicators of physical performance of all subjects were compared before and after intervention to verify the effect of the VIVIFRAIL program. Results At the end of the multicomponent exercise program, Short Physical Performance Battery (SPPB) score as well right and left handgrip (p < 0.05) were significantly increased in frail subjects; right and left handgrip significantly were increased also in robust subjects (p < 0.05). Interestingly, the variation of SPPB was significantly higher in frail compared to robust subjects (p < 0.0001). Moreover, at the end of the program, in frail compared to robust subjects: miR-451a serum concentration was significantly increased (frail: 6.59 × 104; 1.12 × 104–2.5 × 105 c/ng; robust: 2.31 × 104; 1.94 × 103–2.01 × 105 c/ng) (p < 0.05); and 2) miR-93-5p and miR-495-3p serum concentration was reduced, whereas that of miR-155-5p was significantly increased (p < 0.05 in both cases). Serum concentration of miR-93-5p and miR-495-3p was decreased, and that of miR-155-5p was increased at the end of the program in robust subjects alone, statistical significance being reached for miR-93-5p alone (p = 0.02). Conclusion These results suggest that serum miR-451a should be investigated as a potential biomarker for frailty and show that the VIVIFRAIL multicomponent program modulates circulatory miRNAs expression, at least in older adults.

Decreased Serum Levels of the Insulin Resistance-Related microRNA miR-320a in Patients with Polycystic Ovary Syndrome

“…In the whole study cohort, miR-216a and miR-148a showed lower serum levels, whereas miR-93, miR-224 and miR-320a exhibited higher serum levels. MiR-93 is described as consistently measurable circulating microRNA in several metabolism-related studies [28][29][30]. MiR-93 has been shown to be upregulated in women with PCOS and could therefore be a potential biomarker [31].…”

Extracellular MicroRNAs as Potential Biomarkers for Frail Kidney Phenotype: Progresses and Precautions

“…D’Souza and colleagues found that in older adults, resistance exercise consistently modulated skeletal muscle miR-16-5p expressions, whereas protein supplementation also altered muscular miRNA levels [ 38 ]. Another report disclosed that a chronic multicomponent exercise prescription affected serum miR-93-5p, miR-155-5p, and miR-495-3p levels [ 39 ], lending support to the possibility that miRNAs act as surrogates of the multi-dimensional effects resulting in frailty.…”

“…Another recent study disclosed that serum miR-103a-3p, miR-598-3p, and miR-130a-3p levels were differentially expressed between robust and frail individuals with myocardial infarction [ 43 ]. Others pinpointed serum miR-451a levels were increased significantly among frail older adults, serving as a potential frailty biomarker [ 44 ]. An experimental report further showed that extracellular vesicles from young mesenchymal stem cells could prevent frailty and restore epigenetic ages among older littermates through their cargo of miRNA cocktails [ 45 ].…”