Romine Jennifer, Gao Xiang, Xu Xiao-Ming, So Kwok Fai, Chen Jinhui
Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, Guangdong, China.
Neurobiol Aging. 2015 Apr;36(4):1716-1726. doi: 10.1016/j.neurobiolaging.2015.01.003. Epub 2015 Jan 7.
A decrease in neurogenesis in the aged brain has been correlated with cognitive decline. The molecular signaling that regulates age-related decline in neurogenesis is still not fully understood. We found that different subtypes of neural stem cells (NSCs) in the hippocampus were differentially impaired by aging. The quiescent NSCs decreased slowly, although the active NSCs exhibited a sharp and dramatic decline from the ages of 6-9 months and became more quiescent at an early stage during the aging process. The activity of the mammalian target of rapamycin (mTOR) signal pathway is compromised in the NSCs of the aged brain. Activating the mTOR signaling pathway increased NSC proliferation and promoted neurogenesis in aged mice. In contrast, inhibiting the mTOR signaling pathway decreased NSCs proliferation. These results indicate that an age-associated decline in neurogenesis is mainly because of the reduction in proliferation of active NSCs, at least partially because of the compromise in the mTOR signaling activity. Stimulating the mTOR signaling revitalizes the NSCs, restores their proliferation, and enhances neurogenesis in the hippocampus of the aged brain.
老年大脑中神经发生的减少与认知能力下降相关。调节与年龄相关的神经发生衰退的分子信号仍未完全了解。我们发现，海马体中不同亚型的神经干细胞（NSCs）受衰老影响的程度不同。静止的神经干细胞减少缓慢，而活跃的神经干细胞从6至9个月大时开始急剧下降，并在衰老过程的早期变得更加静止。老年大脑神经干细胞中雷帕霉素靶蛋白（mTOR）信号通路的活性受损。激活mTOR信号通路可增加老年小鼠神经干细胞的增殖并促进神经发生。相反，抑制mTOR信号通路会减少神经干细胞的增殖。这些结果表明，与年龄相关的神经发生衰退主要是由于活跃神经干细胞增殖的减少，至少部分是由于mTOR信号活性受损。刺激mTOR信号可使老年大脑海马体中的神经干细胞恢复活力，恢复其增殖，并增强神经发生。
