Bone remodeling is a lifelong process, due to the balanced activity of the osteoblasts (OBs), the bone-forming cells, and osteoclasts (OCs), the bone-resorbing cells. This equilibrium is mainly regulated by the WNT-ß-cathenin pathway and the RANK-RANKL/OPG system, respectively. Bone ageing is a process which normally occurs during life due to the imbalance between bone formation and bone resorption, potentially leading to osteoporosis. Bone loss associated with bone ageing is determined by oxidative stress, the result of the increasing production of reactive oxygen species (ROS). The promotion of physical exercise during growth increases the chances of accruing bone and delaying the onset of osteoporosis. Several studies demonstrate that physical exercise is associated with higher bone mineral density and lower fracture incidence, and the resulting bone mineral gain is maintained with ageing, despite a reduction of physical activity in adulthood. The benefits of exercise are widely recognized, thus physical activity is considered the best non-pharmacologic treatment for pathologies such as osteoporosis, obesity, diabetes and cardiovascular disease. We reviewed the physiological mechanisms which control bone remodeling, the effects of physical activity on bone health, and studies on the impact of exercise in reducing bone ageing.

Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and efficacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine.