Vermeulen C J, Cremers T I F H, Westerink B H C, Van De Zande L, Bijlsma R
Evolutionary Genetics, University of Groningen, NL-9751 NN, Haren, The Netherlands.
Mech Ageing Dev. 2006 Jul;127(7):610-7. doi: 10.1016/j.mad.2006.02.004. Epub 2006 Apr 18.
Among various other mechanisms, genetic differences in the production of reactive oxygen species are thought to underlie genetic variation for longevity. Here we report on possible changes in ROS production related processes in response to selection for divergent virgin lifespan in Drosophila. The selection lines were observed to differ significantly in dopamine levels and melanin pigmentation, which is associated with dopamine levels at eclosion. These findings confirm that variation in dopamine levels is associated with genetic variation for longevity. Dopamine has previously been implied in ROS production and in the occurrence of age-related neurodegenerative diseases. In addition, we propose a possible proximate mechanism by which dopamine levels affect longevity in Drosophila: We tested if increased dopamine levels were associated with a "rate-of-living" syndrome of increased activity and respiration levels, thus aggravating the level of oxidative stress. Findings on locomotor activity and oxygen consumption of short-lived flies were in line with expectations. However, the relation is not straightforward, as flies of the long-lived lines did not show any consistent differences in pigmentation or dopamine levels with respect to the control lines. Moreover, long-lived flies also had increased locomotor activity, but showed no consistent differences in respiration rate. This strongly suggests that the response for increased and decreased lifespan may be obtained by different mechanisms.
在诸多其他机制中,活性氧产生方面的基因差异被认为是寿命遗传变异的基础。在此,我们报告了果蝇中针对不同处女蝇寿命进行选择时,与活性氧产生相关过程可能发生的变化。观察到选择品系在多巴胺水平和黑色素沉着方面存在显著差异,而黑色素沉着与羽化时的多巴胺水平相关。这些发现证实多巴胺水平的变化与寿命的遗传变异有关。多巴胺此前已被认为与活性氧产生以及与年龄相关的神经退行性疾病的发生有关。此外,我们提出了一种多巴胺水平影响果蝇寿命的可能直接机制:我们测试了多巴胺水平升高是否与活动和呼吸水平增加的“生活速率”综合征相关,从而加剧氧化应激水平。短寿命果蝇的运动活动和耗氧量的研究结果符合预期。然而,这种关系并不简单,因为长寿品系的果蝇在色素沉着或多巴胺水平方面与对照品系相比没有表现出任何一致的差异。此外,长寿果蝇的运动活动也增加了,但呼吸速率没有表现出一致的差异。这强烈表明,寿命增加和减少的反应可能是通过不同机制实现的。