Modulation of GDF11 expression and synaptic plasticity by age and training

// Emanuela De Domenico 1,* , Giovanna D’Arcangelo 2,* , Isabella Faraoni 2 , Mattia Palmieri 2 , Virginia Tancredi 2 , Grazia Graziani 2 , Paola Grimaldi 1 and Lucio Tentori 2 1 Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy 2 Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy * These authors have contributed equally to the work and should be considered as equal first authors Correspondence to: Lucio Tentori, email: // Paola Grimaldi, email: // Keywords : GDF11, skeletal muscle, hippocampus, exercise, long-term potentiation, Gerotarget Received : June 16, 2017 Accepted : July 25, 2017 Published : August 03, 2017 Abstract The Growth Differentiation Factor 11 (GDF11) has been controversially involved in the aging/rejuvenation process. To clarify whether GDF11 is differently expressed during aging, we have evaluated GDF11 levels in skeletal muscles and hippocampi of young and old mice, sedentary or subjected to a 12-weeks triweekly training protocol. The results of real-time PCR and Western blot analyses indicate that skeletal muscles of sedentary old mice express higher levels of GDF11 compared to young animals ( p < 0.05). Conversely, in hippocampi no significant differences of GDF11 expression are detected. Analysis of long-term potentiation, a synaptic plasticity phenomenon, reveals that population spikes i n response to a tetanic stimulus are significantly higher in sedentary young mice than in old animals ( p < 0.01). Training induces a significant improvement of long-term potentiation in both young and old animals ( p < 0.05), an increase ( p < 0.05) of skeletal muscle GDF11 levels in young mice and a reduction of GDF11 expression in hippocampi of old mice ( p < 0.05). Overall, data suggest that GDF11 can be considered an aging biomarker for skeletal muscles. Moreover, physical exercise has a positive impact on long-term potentiation in both young and old mice, while it has variable effects on GDF11 expression depending on age and on the tissue analyzed.