Sarcopenia associates with SNAP-25 SNPs and a miRNAs profile which is modulated by structured rehabilitation treatment

Abstract

Background: Sarcopenia is a loss of muscle mass and strength causing disability, morbidity, and mortality in older adults, which is characterized by alterations of the neuromuscular junctions (NMJs). SNAP-25 is essential for the maintenance of NMJ integrity, and the expression of this protein was shown to be modulated by the SNAP-25 rs363050 polymorphism and by a number of miRNAs. Methods: We analysed these parameters in a cohort of sarcopenic patients undergoing structured rehabilitation. The rs363050 genotype frequency distribution was analyzed in 177 sarcopenic patients and 181 healthy controls (HC). The concentration of seven miRNAs (miR-451a, miR-425-5p, miR155-5p, miR-421-3p, miR-495-3p, miR-744-5p and miR-93-5p), identified by mouse brain miRNome analysis to be differentially expressed in wild type compared to SNAP-25± heterozygous mice, was analyzed as well by droplet digital PCR (ddPCR) in a subgroup of severe sarcopenic patients undergoing rehabilitation. Results: The SNAP-25 rs363050 AA genotype was significantly more common in sarcopenic patients compared to HC (pc = 0.01); miR-451a was significantly up-regulated in these patients before rehabilitation. Rehabilitation modified miRNAs expression, as miR-155-5p, miR-421-3p, miR-451a, miR-425-5p, miR-744-5p and miR-93-5p expression was significantly up-regulated (p < 0.01), whereas that of miR-495-3p was significantly down-regulated (p < 0.001) by rehabilitation. Notably, rehabilitation-associated improvement of the muscle-skeletal SPPB score was significantly associated with the reduction of miR-451a expression. Conclusion: These results support the hypothesis of a role for SNAP-25 in sarcopenia and suggest SNAP-25-associated miRNAs as circulatory biomarkers of rehabilitative outcome for sarcopenia.