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Sarcopenia associates with SNAP-25 SNPs and a miRNAs profile which is modulated by structured rehabilitation treatment.
Agostini, Simone; Mancuso, Roberta; Costa, Andrea Saul; Guerini, Franca Rosa; Trecate, Fabio; Miglioli, Rossella; Menna, Elisabetta; Arosio, Beatrice; Clerici, Mario.
Afiliación
  • Agostini S; IRCCS Fondazione Don Carlo Gnocchi ONLUS, P.zza Morandi, 3, 20100, Milan, Italy. sagostini@dongnocchi.it.
  • Mancuso R; IRCCS Fondazione Don Carlo Gnocchi ONLUS, P.zza Morandi, 3, 20100, Milan, Italy.
  • Costa AS; IRCCS Fondazione Don Carlo Gnocchi ONLUS, P.zza Morandi, 3, 20100, Milan, Italy.
  • Guerini FR; IRCCS Fondazione Don Carlo Gnocchi ONLUS, P.zza Morandi, 3, 20100, Milan, Italy.
  • Trecate F; IRCCS Fondazione Don Carlo Gnocchi ONLUS, P.zza Morandi, 3, 20100, Milan, Italy.
  • Miglioli R; IRCCS Fondazione Don Carlo Gnocchi ONLUS, P.zza Morandi, 3, 20100, Milan, Italy.
  • Menna E; CNR-Institute of Neuroscience, Milan, Italy.
  • Arosio B; Humanitas Clinical and Research Center-IRCCS, via Manzoni 56, 20089, Rozzano, MI, Italy.
  • Clerici M; Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
J Transl Med ; 19(1): 315, 2021 07 21.
Article en En | MEDLINE | ID: mdl-34289870
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: MicroARNs / Sarcopenia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Animals / Humans Idioma: En Revista: J Transl Med Año: 2021 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: MicroARNs / Sarcopenia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Animals / Humans Idioma: En Revista: J Transl Med Año: 2021 Tipo del documento: Article País de afiliación: Italia