Department of Health and Exercise Science, Colorado State University, 220 Moby B Complex, Fort Collins, CO 80523-1582.
J Gerontol A Biol Sci Med Sci. 2013 Dec;68(12):1493-501. doi: 10.1093/gerona/glt047. Epub 2013 May 8.
Chronic inhibition of the protein synthesis regulator mTORC1 through rapamycin extends life span in mice, with longer extension in females than in males. Whether rapamycin treatment inhibits protein synthesis or whether it does so differently between sexes has not been examined. UM-HET3 mice were fed a control or rapamycin-supplemented (Rap) diet for 12 weeks. Protein synthesis in mixed, cytosolic (cyto), and mitochondrial (mito) fractions and DNA synthesis and mTORC1 signaling were determined in skeletal muscle, heart, and liver. In both sexes, mito protein synthesis was maintained in skeletal muscle from Rap despite decreases in mixed and cyto fractions, DNA synthesis, and rpS6 phosphorylation. In the heart, no change in protein synthesis occurred despite the decreased DNA synthesis. In the heart and liver, Rap males were more sensitive to mTORC1 inhibition than Rap females. In conclusion, we show changes in protein synthesis and mTORC1 signaling that differ by sex and tissue.
雷帕霉素通过慢性抑制蛋白合成调节因子 mTORC1 延长了小鼠的寿命，且雌性的延长效果优于雄性。雷帕霉素治疗是否抑制蛋白合成，以及其在两性之间的抑制方式是否不同，这些问题尚未得到检验。UM-HET3 小鼠连续喂食对照饮食或雷帕霉素补充（Rap）饮食 12 周。检测了骨骼肌、心脏和肝脏中混合、胞浆（cyto）和线粒体（mito）部分的蛋白合成以及 DNA 合成和 mTORC1 信号。尽管混合和胞浆部分、DNA 合成和 rpS6 磷酸化减少，雷帕霉素仍维持了骨骼肌中线粒体蛋白的合成。心脏中尽管 DNA 合成减少，但蛋白合成没有变化。心脏和肝脏中，雷帕霉素雄性对 mTORC1 抑制的敏感性高于雷帕霉素雌性。总之，我们发现蛋白合成和 mTORC1 信号的变化因性别和组织而异。
