Sarcopenia refers to a condition of progressive loss of skeletal muscle mass and function associated with a higher risk of falls and fractures in older adults. Musculoskeletal aging leads to reduced muscle mass and strength, affecting the quality of life in elderly people. In recent years, several studies contributed to improve the knowledge of the pathophysiological alterations that lead to skeletal muscle dysfunction; however, the molecular mechanisms underlying sarcopenia are still not fully understood. Muscle development and homeostasis require a fine gene expression modulation by mechanisms in which microRNAs (miRNAs) play a crucial role. miRNAs modulate key steps of skeletal myogenesis including satellite cells renewal, skeletal muscle plasticity, and regeneration. Here, we provide an overview of the general aspects of muscle regeneration and miRNAs role in skeletal mass homeostasis and plasticity with a special interest in their expression in sarcopenia and skeletal muscle adaptation to exercise in the elderly.

Physical exercise is known to promote beneficial effects on overall health, counteracting risks related to degenerative diseases. MicroRNAs (miRNAs), short non-coding RNAs affecting the expression of a cell’s transcriptome, can be modulated by different stimuli. Yet, the molecular effects on osteogenic differentiation triggered by miRNAs upon physical exercise are not completely understood. In this study, we recruited 20 male amateur runners participating in a half marathon. Runners’ sera, collected before (PRE RUN) and after (POST RUN) the run, were added to cultured human mesenchymal stromal cells. We then investigated their effects on the modulation of selected miRNAs and the consequential effects on osteogenic differentiation. Our results showed an increased expression of miRNAs promoting osteogenic differentiation (miR-21-5p, miR-129-5p, and miR-378-5p) and a reduced expression of miRNAs involved in the adipogenic differentiation of progenitor cells (miR-188-5p). In addition, we observed the downregulation of PTEN and SMAD7 expression along with increased AKT/pAKT and SMAD4 protein levels in MSCs treated with POST RUN sera. The consequent upregulation of RUNX2 expression was also proven, highlighting the molecular mechanisms by which miR-21-5p promotes osteogenic differentiation. In conclusion, our work proposes novel data, which demonstrate how miRNAs may regulate the osteogenic commitment of progenitor cells in response to physical exercise.

The association of lysosomal dysfunction and neurodegeneration has been documented in several neurodegenerative diseases, including Alzheimer’s Disease (AD). Herein, we investigate the association of lysosomal enzymes with AD at different stages of progression of the disease (mild and severe) or with mild cognitive impairment (MCI). We conducted a screening of two classes of lysosomal enzymes: glycohydrolases (β-Hexosaminidase, β-Galctosidase, β-Galactosylcerebrosidase, β-Glucuronidase) and proteases (Cathepsins S, D, B, L) in peripheral blood samples (blood plasma and PBMCs) from mild AD, severe AD, MCI and healthy control subjects. We confirmed the lysosomal dysfunction in severe AD patients and added new findings enhancing the association of abnormal levels of specific lysosomal enzymes with the mild AD or severe AD, and highlighting the difference of AD from MCI. Herein, we showed for the first time the specific alteration of β-Galctosidase (Gal), β-Galactosylcerebrosidase (GALC) in MCI patients. It is notable that in above peripheral biological samples the lysosomes are more sensitive to AD cellular metabolic alteration when compared to levels of Aβ-peptide or Tau proteins, similar in both AD groups analyzed. Collectively, our findings support the role of lysosomal enzymes as potential peripheral molecules that vary with the progression of AD, and make them useful for monitoring regenerative medicine approaches for AD.

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes. While current evidence supports the association between low vitamin D levels and increased cardiovascular mortality, this work contributes novel insights by proposing tailored strategies for supplementation, particularly for high-risk subgroups. Practical recommendations for implementing these strategies in clinical practice are also discussed, providing a framework for optimizing cardiovascular outcomes through individualized vitamin D management.