J Neurosci:节食可延缓老年动物行为退化
中国科学报 · 2014/04/14
最近,来自中科院上海生科院神经科学研究所蔡时青研究组发现,长寿并不一定能延缓动物的行为退化。同时,节食提高老年动物的行为能力,部分是由于节食提高了五羟色胺和多巴胺功能。相关成果日前在线发表于《神经科学杂志》


中科院上海生科院神经科学研究所蔡时青研究组发现,长寿并不一定能延缓动物的行为退化。同时,节食提高老年动物的行为能力,部分是由于节食提高了五羟色胺和多巴胺功能。相关成果日前在线发表于《神经科学杂志》(The Journal of Neuroscience)。

据了解,目前衰老领域的研究主要集中在寿命调节方面,科学家已发现上百个基因可调控动物寿命。行为和认知功能退化也是动物和人类衰老的重要特征,但延长寿命是否必然延缓衰老引起的行为退化是一个非常关键但尚未破解的问题。

此次研究人员对长寿基因是否影响五羟色胺和多巴胺功能以及衰老过程中动物的行为退化开展了深入研究。研究发现,不同的长寿基因对五羟色胺和多巴胺功能的影响不尽相同,胰岛素信号通路中的长寿基因不影响五羟色胺和多巴胺水平以及相应的行为退化过程。节食这种广为人知的长寿方式,则可以很好地维持老年动物的五羟色胺和多巴胺水平,进而延缓咽喉肌肉跳动、雄性交配能力等行为的退化。

进一步研究发现,在衰老过程中,氧化自由基的积累导致五羟色胺和多巴胺共同的合成酶BAS-1(多巴脱羧酶)表达量下降,这是神经元中五羟色胺和多巴胺含量降低的主要原因。和节食相关的长寿基因pha-4则通过上调SOD-1和Catalase等蛋白的表达,提高神经元清除氧化自由基能力,进而上调BAS-1表达,维持五羟色胺和多巴胺水平。有趣的是,在老年时期提高内源五羟色胺或多巴胺水平,可延缓野生型和长寿线虫daf-2(e1370)的行为能力退化。同时,提高老年时期五羟色胺水平也可延长线虫寿命。

专家表示,该研究初步揭示了动物行为能力随衰老退化的分子神经机制,为提高老年人口的健康和生活质量提供了新线索。
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    Aging is accompanied with behavioral and cognitive decline. Changes in the neurotransmitter level are associated with the age-related behavioral deterioration, but whether well-known longevity manipulations affect the function of neurotransmitter system in aging animals is largely unclear. Here we report that serotonin (5-HT) and dopamine (DA) level decrease with age in C. elegans. The reduction results in downregulation of the activity of neurons controlled by 5-HT/DA signaling, and deterioration of some important behaviors, including pharyngeal pumping, food-induced slowing responses, and male mating. Longevity manipulations differentially affect the age-related decline in neuronal level of 5-HT/DA. The reduction and resultant behavioral deterioration occur in long-lived worms with defective insulin signaling [daf-2(e1370), age-1(hx546)] or mitochondria function [isp-1(qm150), tpk-1(qm162)], but not in long-lived worms with dietary restriction eat-2(ad1116). A reduced expression level of dopa decarboxylase BAS-1, the shared enzyme for 5-HT/DA synthesis, is responsible for the decline in 5-HT/DA levels. RNAi assay revealed that the sustained 5-HT/DA level in neurons of aged eat-2(ad1116) worms requires PHA-4 and its effectors superoxide dismutases and catalases, suggesting the involvement of reactive oxygen species in the 5-HT/DA decline. Furthermore, we found that elevating 5-HT/DA ameliorates age-related deterioration of pharyngeal pumping, food-induced slowing responses, and male mating in both wild-type and daf-2(e1370) worms. Together, dietary restriction preserves healthy behaviors in aged worms at least partially by sustaining a high 5-HT/DA level, and elevating the 5-HT/DA level in wild-type and daf-2(e1370) worms improves their behaviors during aging.

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