Chen Chun-Hao, Chen Yen-Chih, Jiang Hao-Ching, Chen Chung-Kuan, Pan Chun-Liang
Institute of Molecular Medicine, College of Medicine, National Taiwan University, No, 7, Chung-Shan South Rd, Taipei 100, Taiwan.
J Mol Signal. 2013 Dec 10;8(1):14. doi: 10.1186/1750-2187-8-14.
The heterogeneity and multigenetic nature of nervous system aging make modeling of it a formidable task in mammalian species. The powerful genetics, simple anatomy and short life span of the nematode Caenorhabditis elegans offer unique advantages in unraveling the molecular genetic network that regulates the integrity of neuronal structures and functions during aging. In this review, we first summarize recent breakthroughs in the morphological and functional characterization of C. elegans neuronal aging. Age-associated morphological changes include age-dependent neurite branching, axon beading or swelling, axon defasciculation, progressive distortion of the neuronal soma, and early decline in presynaptic release function. We then discuss genetic pathways that modulate the speed of neuronal aging concordant with alteration in life span, such as insulin signaling, as well as cell-autonomous factors that promote neuronal integrity during senescence, including membrane activity and JNK/MAPK signaling. As a robust genetic model for aging, insights from C. elegans neuronal aging studies will contribute to our mechanistic understanding of human brain aging.
神经系统衰老的异质性和多基因特性使得在哺乳动物中对其进行建模成为一项艰巨的任务。线虫秀丽隐杆线虫强大的遗传学、简单的解剖结构和较短的寿命，为揭示衰老过程中调节神经元结构和功能完整性的分子遗传网络提供了独特优势。在这篇综述中，我们首先总结了秀丽隐杆线虫神经元衰老在形态学和功能特征方面的最新突破。与年龄相关的形态学变化包括年龄依赖性的神经突分支、轴突串珠或肿胀、轴突解束、神经元胞体的渐进性变形以及突触前释放功能的早期下降。然后，我们讨论了与寿命改变相一致的调节神经元衰老速度的遗传途径，如胰岛素信号通路，以及在衰老过程中促进神经元完整性的细胞自主因子，包括膜活性和JNK/MAPK信号通路。作为一个强大的衰老遗传模型，秀丽隐杆线虫神经元衰老研究的见解将有助于我们对人类大脑衰老的机制理解。
