Park Hee Ra, Park Mikyung, Kim Hyung Sik, Lee Jaewon
Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan, 609-735 Korea.
Toxicol Res. 2008 Dec;24(4):245-251. doi: 10.5487/TR.2008.24.4.245. Epub 2008 Dec 1.
Dietary restriction (DR) is the most efficacious intervention for retarding the deleterious effects of aging. DR increases longevity, decreases the occurrence and severity of age-related diseases, and retards the physiological decline associated with aging. The beneficial effects of DR have been mostly studied in non-neuronal tissues. However, several studies have showed that DR attenuate neuronal loss after several different insults including exposure to kainate, ischemia, and MPTR Moreover, administration of the non-metabolizable glucose analog 2-deoxy-D-glucose (2DG) could mimic the neuroprotective effect of DR in rodent, presumably by limiting glucose availability at the cellular level. Based on the studies of chemically induced D.R., it has been proposed that the mechanism whereby DR and 2DG protect neurons is largely mediated by stress response proteins such as HSP70 and GRP78 which are increased in neurons of rats and mice fed a DR regimen. In addition, D.R., as mild metabolic stress, could lead to the increased activity in neuronal circuits and thus induce expression of neurotrophic factors. Interestingly, such increased neuronal activities also enhance neurogenesis in the brains of adult rodents. In this review, we focus on what is known regarding molecular mechanisms of the protective role of DR in neurodegenerative diseases and aging process. Also, we propose that DR is a mild cellular stress that stimulates production of neurotrophic factors, which are major regulators of neuronal survival, as well as neurogenesis in adult brain.
饮食限制（DR）是延缓衰老有害影响最有效的干预措施。饮食限制可延长寿命，降低与年龄相关疾病的发生率和严重程度，并延缓与衰老相关的生理衰退。饮食限制的有益作用大多在非神经组织中进行了研究。然而，多项研究表明，饮食限制可减轻包括暴露于红藻氨酸、缺血和MPTP等几种不同损伤后的神经元损失。此外，给予不可代谢的葡萄糖类似物2-脱氧-D-葡萄糖（2DG）可模拟饮食限制在啮齿动物中的神经保护作用，这可能是通过在细胞水平限制葡萄糖供应来实现的。基于化学诱导饮食限制的研究，有人提出饮食限制和2DG保护神经元的机制很大程度上是由应激反应蛋白介导的，如HSP70和GRP78，在采用饮食限制方案喂养的大鼠和小鼠的神经元中这些蛋白会增加。此外，饮食限制作为一种轻度代谢应激，可导致神经回路活动增加，从而诱导神经营养因子的表达。有趣的是，这种增加的神经元活动也会增强成年啮齿动物大脑中的神经发生。在这篇综述中，我们重点关注饮食限制在神经退行性疾病和衰老过程中的保护作用的分子机制。此外，我们提出饮食限制是一种轻度细胞应激，可刺激神经营养因子的产生，这些因子是神经元存活以及成年大脑神经发生的主要调节因子。
