Department of Biological Sciences, Southern Methodist University, 6501 Airline Drive, 238-DLS, Dallas, TX 75275, USA.
Mech Ageing Dev. 2012 Nov-Dec;133(11-12):637-46. doi: 10.1016/j.mad.2012.08.004. Epub 2012 Aug 30.
In order to understand the molecular mechanisms of longevity regulation, we recently performed a screen designed to enrich for genes common to several longevity interventions. Using this approach, we identified the Drosophila melanogaster gene takeout. takeout is upregulated in a variety of long-lived flies, and extends life span when overexpressed. Here, we investigate the mechanisms of takeout-dependent longevity. takeout overexpression specifically in the fat body is sufficient to increase fly longevity and is additive to the longevity effects of Dietary Restriction. takeout long-lived flies do not show phenotypes often associated with increased longevity, such as enhanced stress resistance or major metabolic abnormalities. However, males exhibit greatly diminished courtship behavior, leading to a reduction in fertility. Interestingly, takeout contains a binding domain for Juvenile Hormone, a fly hormone that plays a role in the regulation of developmental transitions. Importantly, the longevity and courtship phenotypes of takeout overexpressing flies are reversed by treatment with the Juvenile Hormone analog methoprene. These data suggest that takeout is a key player in the tradeoff-switch between fertility and longevity. takeout may control fertility via modulation of courtship behavior. This regulation may occur through Juvenile Hormone binding to takeout and a subsequent reduction in Juvenile Hormone signaling activity.
为了理解长寿调控的分子机制，我们最近进行了一项筛选，旨在富集几种长寿干预措施中常见的基因。通过这种方法，我们鉴定了黑腹果蝇的 takeout 基因。在多种长寿果蝇中，takeout 的表达上调，并在过表达时延长寿命。在这里，我们研究了 takeout 依赖性长寿的机制。在脂肪体中特异性过表达 takeout 足以增加果蝇的寿命，并且与饮食限制的长寿效应具有加性。takeout 长寿的果蝇没有表现出与寿命延长相关的表型，例如增强的应激抗性或主要的代谢异常。然而，雄性表现出极大地减少的求偶行为，导致繁殖力降低。有趣的是，takeout 包含一个结合域，用于保幼激素，一种在发育过渡调节中起作用的果蝇激素。重要的是，用保幼激素类似物 methoprene 处理可逆转过度表达 takeout 的果蝇的长寿和求偶表型。这些数据表明，takeout 是生育力和长寿之间权衡开关的关键参与者。takeout 可能通过调节求偶行为来控制生育力。这种调节可能通过保幼激素与 takeout 的结合以及随后降低保幼激素信号活性来发生。
