Division of Exercise Physiology, West Virginia University School of Medicine, PO Box 9227, 1 Medical Center Drive, Morgantown, WV 26506, USA.
J Gerontol A Biol Sci Med Sci. 2010 Apr;65(4):335-43. doi: 10.1093/gerona/glq005. Epub 2010 Feb 5.
This investigation examined Akt-FOXO3A signaling in young women (YW) and old women (OW) before and after 12 weeks of high-intensity resistance training. Muscle biopsies were taken from the vastus lateralis before and immediately after resistance exercise (RE) in the untrained and trained states. In response to RE in YW and OW, phospho Akt Thr308 increased in untrained and trained states, with no change on Ser473 site. FOXO3A-Ser253 site was dephosphorylated in untrained state among YW and OW, and nuclear phospho-FOXO3A increased mainly in YW in trained state. In the basal state, OW displayed lower cytosolic phospho-FOXO3A before training, higher total nuclear FOXO3A, and a trend for higher nuclear-to-cytosolic FOXO3A ratio versus YW after 12 weeks. Basal level MuRF-1 and myostatin mRNA decreased in YW, while OW increased myostatin mRNA after 12-weeks. These data suggest that FOXO3A signaling and FOXO3A-related target gene expression are altered in OW and may partially explain the attenuated training adaptations previously reported in these octogenarian women.
本研究旨在探讨高强度抗阻训练对年轻女性（YW）和老年女性（OW） Akt-FOXO3A 信号通路的影响。分别在未训练和训练状态下，于股外侧肌采集抗阻运动（RE）前后的肌肉活检样本。结果显示，YW 和 OW 在未训练和训练状态下，磷酸化 Akt Thr308 增加，而 Ser473 位点无变化。在未训练状态下，YW 和 OW 的 FOXO3A-Ser253 位点去磷酸化，而在训练状态下，主要是 YW 的核磷酸化 FOXO3A 增加。在基础状态下，OW 的胞质磷酸化 FOXO3A 水平低于 YW，总核 FOXO3A 水平较高，核质比也高于 YW。基础状态下，YW 的 MuRF-1 和肌肉生长抑制素（myostatin）mRNA 减少，而 OW 在 12 周后增加了 myostatin mRNA。这些数据表明，OW 的 FOXO3A 信号通路和 FOXO3A 相关靶基因表达发生改变，这可能部分解释了之前报道的这些 80 岁以上女性训练适应能力减弱的原因。
