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The finding of molecules associated with aging is important for the prevention of chronic degenerative diseases and for longevity strategies. MicroRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and miR-146b-5p has been shown to be involved in different degenerative diseases. However, miR-146b-5p modulation has not been evaluated in mesenchymal stem cells (MSCs) commitment or during aging. Therefore, the modulation of miR-146b-5p in the commitment and differentiation of mesenchymal cells as well as during maturation and aging in zebrafish model were analyzed. In addition, circulating miR-146b-5p was evaluated in human subjects at different age ranges. Thus, the role of physical activity in the modulation of miR-146b-5p was also investigated. To achieve these aims, RT (real-time)-PCR, Western blot, cell transfections, and three-dimensional (3D) culture techniques were applied. Our findings show that miR-146b-5p expression drives MSCs to adipogenic differentiation and increases during zebrafish maturation and aging. In addition, miR-146b-5p expression is higher in females compared to males and it is associated with the aging in humans. Interestingly, we also observed that the physical activity of walking downregulates circulating miR-146b-5p levels in human females and increases the number of chondroprogenitors. In conclusion, miR-146b-5p can be considered an age-related marker and can represent a useful marker for identifying strategies, such as physical activity, aimed at counteracting the degenerative processes of aging.

Background: There is increasing evidence of the influence of the oropharyngeal stimulations on the autonomic nervous system and an easy approach to evaluate the balance between parasympathetic and sympathetic system is the measurement of the pupil diameter. The aim of this analytic observational study is to define the effects of clenching and swallowing on pupil diameter, and how an oral appliance can affect the outcome of these tasks, to establish their influence on the sympathetic-parasympathetic balance., Methods: We measured the pupil diameter in 30 healthy subjects during clenching and swallowing, both with and without oral appliance. We compared the results with the mandibular rest position. The respective positions with and without oral appliance were also compared., Results: Pupillometry showed a mydriatic effect of swallowing (rest 6.94 mm, swallowing 7.26 mm, P=0.04) and oral appliance, more relevant in scotopic conditions. On the contrary, clenching seemed to enhance miosis, especially in intense brightness condition (rest 3.95 mm, clenching 3.83 mm, P=0.02)., Conclusions: Swallowing and oral appliance facilitate the sympathetic system, while clenching activates the parasympathetic branch. We argue that probably the locus coeruleus is the main hub. These results could have practical implications in bruxism physiology, because it could be an attempt to counteract the activation of the sympathetic system.