De Domenico Emanuela, D'Arcangelo Giovanna, Faraoni Isabella, Palmieri Mattia, Tancredi Virginia, Graziani Grazia, Grimaldi Paola, Tentori Lucio
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Oncotarget. 2017 Aug 3;8(35):57991-58002. doi: 10.18632/oncotarget.19854. eCollection 2017 Aug 29.
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 ( < 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 ( < 0.01). Training induces a significant improvement of long-term potentiation in both young and old animals ( < 0.05), an increase ( < 0.05) of skeletal muscle GDF11 levels in young mice and a reduction of GDF11 expression in hippocampi of old mice ( < 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.
生长分化因子11(GDF11)在衰老/年轻化过程中一直存在争议。为了阐明GDF11在衰老过程中是否存在差异表达,我们评估了年轻和老年小鼠(久坐不动或接受为期12周、每周三次的训练方案)骨骼肌和海马体中的GDF11水平。实时PCR和蛋白质印迹分析结果表明,久坐不动的老年小鼠骨骼肌中GDF11的表达水平高于年轻动物(P<0.05)。相反,在海马体中未检测到GDF11表达的显著差异。对突触可塑性现象——长时程增强的分析表明,久坐不动的年轻小鼠对强直刺激的群体峰电位显著高于老年动物(P<0.01)。训练可显著改善年轻和老年动物的长时程增强(P<0.05),使年轻小鼠骨骼肌GDF11水平升高(P<0.05),并使老年小鼠海马体中GDF11表达降低(P<0.05)。总体而言,数据表明GDF11可被视为骨骼肌的衰老生物标志物。此外,体育锻炼对年轻和老年小鼠的长时程增强均有积极影响,但其对GDF11表达的影响因年龄和所分析的组织而异。