Apple Deana M, Mahesula Swetha, Fonseca Rene Solano, Zhu Chang, Kokovay Erzsebet
Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
The Barshop Institute on Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Aging (Albany NY). 2019 Jan 8;11(1):115-126. doi: 10.18632/aging.101731.
The brain can generate new neurons from neural stem cells throughout life. However, the capacity for neurogenesis declines with age, reducing the potential for learning and repair. We explored the effects of calorie restriction, an established anti-aging intervention, on neural stem cells in the subventricular zone of young and aged mice. Calorie restriction transiently enhanced proliferation of neural progenitor cells in young, but not aged mice. However, calorie restriction prevented the age-related loss of neurogenesis in the aged brain. Calorie-restricted mice showed enhanced olfactory memory compared with fed controls, suggesting that calorie restriction can produce functional improvements in the aged brain. Calorie restriction also mitigated the age-related activation of microglia and subsequent increase in pro-inflammatory cytokines. Likewise, calorie restriction prevented increases in senescent cells normally observed in the subventricular zone in aged mice, further protecting this neurogenic niche from pro-inflammatory signals. Together, these data suggest that calorie restriction protects the subventricular zone microenvironment from age-related inflammation, thereby preserving neurogenesis into old age.
大脑在一生中都能从神经干细胞生成新的神经元。然而，神经发生的能力会随着年龄的增长而下降，从而降低学习和修复的潜力。我们研究了热量限制（一种已确立的抗衰老干预措施）对年轻和老年小鼠脑室下区神经干细胞的影响。热量限制短暂地增强了年轻小鼠而非老年小鼠神经祖细胞的增殖。然而，热量限制可防止老年大脑中与年龄相关的神经发生丧失。与进食的对照组相比，热量限制的小鼠表现出增强的嗅觉记忆，这表明热量限制可在老年大脑中产生功能改善。热量限制还减轻了与年龄相关的小胶质细胞激活以及随后促炎细胞因子的增加。同样，热量限制可防止老年小鼠脑室下区通常观察到的衰老细胞增加，进一步保护这个神经发生微环境免受促炎信号的影响。总之，这些数据表明热量限制可保护脑室下区微环境免受与年龄相关的炎症影响，从而在老年期维持神经发生。
