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 in 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.
Highlights
The growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGFβ) superfamily, homologous to another muscle-derived hormone, myostatin (MSTN)
In skeletal muscles no significant differences in GDF11 expression were found between sedentary and trained old mice (Figure 6). It is still controversial whether tissue levels of GDF11 protein expression are age-related
In the current study we provide evidence, by using an antibody which recognizes GDF11 and does not cross react with MSTN, that this protein is expressed at higher levels in the skeletal muscle tissue of old mice compared to young animals independently of sex and strain
Summary
The growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGFβ) superfamily, homologous to another muscle-derived hormone, myostatin (MSTN). Initial studies in rodent models exploiting heterochronic parabiosis (in which circulatory systems of young and aged animals are connected) or using recombinant protein treatment, identified GDF11 as a molecule capable of rejuvenating cerebral, cardiac, skeletal muscle functions and attributed the diminished regenerative capacity of skeletal or cardiac muscle and brain of old mice to the decrease of GDF11 serum levels [11,12,13]. Further studies are needed to evaluate whether young and old individuals have a different GDF11 protein expression in tissues (e.g., skeletal muscle, hippocampus), and to clarify the actual role of GDF11 in the regulation of rejuvenation processes and longevity. The present study is an attempt to clarify, in a murine model, whether GDF11 expression in skeletal muscle and hippocampal tissues undergoes modulation during the aging process and whether training modulates GDF11 expression and LTP
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