Demontis Fabio, Patel Vishal K, Swindell William R, Perrimon Norbert
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Developmental Biology, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Cell Rep. 2014 Jun 12;7(5):1481-1494. doi: 10.1016/j.celrep.2014.05.001. Epub 2014 May 29.
Recent evidence indicates that skeletal muscle influences systemic aging, but little is known about the signaling pathways and muscle-released cytokines (myokines) responsible for this intertissue communication. Here, we show that muscle-specific overexpression of the transcription factor Mnt decreases age-related climbing defects and extends lifespan in Drosophila. Mnt overexpression in muscle autonomously decreases the expression of nucleolar components and systemically decreases rRNA levels and the size of the nucleolus in adipocytes. This nonautonomous control of the nucleolus, a regulator of ribosome biogenesis and lifespan, relies on Myoglianin, a myokine induced by Mnt and orthologous to human GDF11 and Myostatin. Myoglianin overexpression in muscle extends lifespan and decreases nucleolar size in adipocytes by activating p38 mitogen-activated protein kinase (MAPK), whereas Myoglianin RNAi in muscle has converse effects. Altogether, these findings highlight a key role for myokine signaling in the integration of signaling events in muscle and distant tissues during aging.
近期证据表明，骨骼肌会影响全身衰老，但对于负责这种组织间通讯的信号通路和肌肉分泌的细胞因子（肌动蛋白）却知之甚少。在此，我们表明转录因子Mnt在肌肉中的特异性过表达可减少与衰老相关的攀爬缺陷，并延长果蝇的寿命。肌肉中Mnt的过表达自主降低核仁成分的表达，并系统性地降低脂肪细胞中rRNA水平和核仁大小。对核仁（核糖体生物发生和寿命的调节因子）的这种非自主控制依赖于Myoglianin，这是一种由Mnt诱导且与人类GDF11和肌肉生长抑制素直系同源的肌动蛋白。肌肉中Myoglianin的过表达通过激活p38丝裂原活化蛋白激酶（MAPK）来延长寿命并减小脂肪细胞中的核仁大小，而肌肉中Myoglianin的RNA干扰则产生相反的效果。总之，这些发现突出了肌动蛋白信号在衰老过程中整合肌肉和远处组织信号事件中的关键作用。
