PDF(Pubmed)
Abstract：
Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan.
摘要：
减少的胰岛素/IGF样信号（IIS）在改善模型生物的寿命和一些健康跨度方面起着进化上保守的作用。最近的研究,然而,发现延长寿命和行为健康之间存在脱节。我们先前已经表明，果蝇神经元中IIS的减少会延长女性的寿命，但不会改善负的地理轴衰老，并且对两性的探索性步行衰老都有不利影响。我们假设单个神经元亚型对IIS变化的反应不同，因此，泛神经元IIS减少的行为结果是积极的平衡，负面和中性功能效应。为了进一步了解神经元中减少的IIS如何独立地调节寿命和运动行为衰老，我们在单个神经元亚型中选择性地表达了显性阴性胰岛素受体转基因，并测量了对寿命的影响和运动衰老的两种措施。负地理定位和探索性行走。胆碱能IIS减少，GABA能,多巴胺能,谷氨酸能,发现八胺能神经元对寿命和运动衰老没有影响或有害影响。然而,选择性减少血清素能神经元中的IIS导致女性寿命延长，而对运动衰老没有影响。这些数据表明，各个神经元亚型对IIS在寿命和运动衰老的调节中的变化有不同的反应，并确定胰岛素受体在5-羟色胺能神经元调节寿命中的特定作用。
