Leader: Marco Narici (UNIPD); Other collaborator(s):
We plan to investigate how physical activity affects the trajectories of neuromuscular aging. Individuals aged 25-80 + years will be studied, stratified according to the level of physical activity (number of daily steps) and sarcopenic profile (according to the 2021 EWGSOP2 sarcopenia definition) . Biomarkers will be evaluated for: 1) stability of the neuromuscular junction, NMJ (c-terminal agrin fragment, serum), 2) axonal integrity (neurofilament light chain, serum), 3) denervation in muscle micro-samples (25mg): neural cell adhesion molecule (NCAM), voltage-gated sodium channel (NAV1.5), 4) expression of genes involved in NMJ integrity through RNA sequencing, 5) NMJ transmission efficiency ( by intramuscular EMG): Jiggle and Jitter, number and size of motor units, frequency of motor unit discharge and recruitment threshold, 6) dynamic balance, 7) muscle strength (handgrip and quadriceps) and walking speed, 8) muscle mass and architecture through DEXA and ultrasound.
Brief description of the activities and of the intermediate results: We have successfully recruited 180 male and female participants aged 25-91 who undewent medical screening following the exclusion criteria of the sudy. Those admitted to the study underwent testing for sarcopenia (according tho the EWGSOP2 guidelines), for physical activity level based on 7-day accelerometry and for cognitive capacity using the Montreal Cognitive Assessment (MoCA). Each individual, following informed consent, underwent the following tests: 1) muscle ultrasound for muscle size determination, 2) dynamic balance on a basculating platform, 3) voluntary muscle activation capacity, 4) intramuscular EMG (iEMG) and high -density EMG (HD-EMG), 5) venous blood sample, 6) vastus lateralis muscle biopsy. Blood samples have been separated into plasma and serum aliquots and stored at -80 for later analysis. Muscle biopsy samples have been divided into four portions, one for biochemistry, one for NMJ morphology, one for histochemistry (in OCT) and one for spatial transcriptomics. Samples have been stored at -80 for later analysis.
Brief description of the activities and of the intermediate results: We have successfully recruited 180 male and female participants aged 25-91 years who undewent medical screening following the exclusion criteria of the sudy. Those admitted to the study underwent testing for sarcopenia (according tho the EWGSOP2 guidelines), for physical activity level based on 7-day accelerometry and for cognitive capacity using the Montreal Cognitive Assessment (MoCA). Each individual, following informed consent, underwent the following tests: 1) muscle ultrasound for muscle size determination, 2) dynamic balance on a basculating platform, 3) voluntary muscle activation capacity, 4) intramuscular EMG (iEMG) and high -density EMG (HD-EMG) have been performed for the study of neuromuscular junction efficiency and motor unit recruitment properties according to patients' age 5) venous blood sample, 6) vastus lateralis muscle biopsy. Blood samples have been separated into plasma and serum aliquots and stored at -80 for later analysis. Muscle biopsy samples have been divided into four portions, one for biochemistry, one for NMJ morphology, one for histochemistry (in OCT) and one for spatial transcriptomics. Samples have been stored at -80 for later analysis.
Brief description of the activities and of the intermediate results: We have successfully recruited 180 male and female participants aged 25-91 years who undewent medical screening following the exclusion criteria of the sudy. Those admitted to the study underwent testing for sarcopenia (according tho the EWGSOP2 guidelines), for physical activity level based on 7-day accelerometry and for cognitive capacity using the Montreal Cognitive Assessment (MoCA). Each individual, following informed consent, underwent the following tests: 1) muscle ultrasound for muscle size determination, 2) dynamic balance on a basculating platform, 3) voluntary muscle activation capacity, 4) intramuscular EMG (iEMG) and high -density EMG (HD-EMG) have been performed for the study of neuromuscular junction efficiency and motor unit recruitment properties according to patients' age 5) venous blood sample, 6) vastus lateralis muscle biopsy, 7) measurements of strength (handgrip), body composition (DXA) and functional performance to assess sarcopenia and stratify enrolled population accordingly, 8) assess physical activity via accelerometers. Blood samples have been separated into plasma and serum aliquots and stored at -80 for later analysis. Muscle biopsy samples have been divided into four portions, one for biochemistry, one for NMJ morphology, one for histochemistry (in OCT) and one for spatial transcriptomics. Samples have been stored at -80 for later analysis.
Scientific papers:
- E. Motanova, M. Pirazzini, S. Negro, O. Rossetto, M. Narici. Impact of ageing and disuse on neuromuscular junction and mitochondrial function and morphology: current evidence and controversies. Ageing Res Rev 102:102586, 2024
- F. Sarto, M.V. Franchi, J.S. McPhee, D.W. Stashuk, M. Paganini, E. Monti, M. Rossi, G. Sirago, S. Zampieri, E.S. Motanova, G. Valli, T. Moro, A. Paoli, R. Bottinelli, M.A. Pellegrino, G. De Vito, H.M. Blau, M.V. Narici. Neuromuscular impairment at different stages of human sarcopenia. J Cachexia Sarcopenia Muscle 15(5):1797-1810, 2024