Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA.
Exp Gerontol. 2011 May;46(5):363-8. doi: 10.1016/j.exger.2010.12.002. Epub 2010 Dec 25.
It has been almost two decades since dietary restriction was first shown to increase Drosophila lifespan. Since then, understanding this phenomenon advanced as groups worked to identify what quality of restricted diet matters: calories or a specific nutrient. The problem is complex because is it difficult to measure what a fly actually consumes. A powerful solution uses the geometric framework of nutrition where diets in many combinations can be tested for their effects on lifespan and reproduction while measuring intake. Applied to Drosophila, it is now clear that specific nutrients, not calories, mediate longevity. The geometric framework also reveals a nutritional basis for the trade-off between reproduction and lifespan. This complements a stable-isotope analysis that tracked the allocation of nitrogen, carbon and essential amino acids into eggs versus reproduction. Together, these studies show that it is not possible to explain how DR extends lifespan through a mechanism were resources are simply reallocated to somatic maintenance away from reproduction. Although promising in principle, genetic analysis of DR mechanisms has had limited success. To be productive, studies must include enough diets at appropriate concentrations. In reviewing the best data, there is little evidence to date for any gene to be required for DR to increase Drosophila lifespan, including insulin signaling or 4eBP. Strong analyses of genes required for DR should be a priority in future research with Drosophila and this may be made most robust by considering the effect of mutants in the context of the geometric framework.
自限制饮食首次被证明能延长果蝇寿命以来，已经过去了将近 20 年。从那时起，随着研究小组努力确定限制饮食中重要的是哪一种质量：卡路里还是特定营养素，人们对这一现象的理解有了进展。问题很复杂，因为很难衡量果蝇实际摄入了什么。一个强大的解决方案是利用营养的几何框架，在这个框架中，可以测试许多组合的饮食对寿命和繁殖的影响，同时测量摄入量。将其应用于果蝇，现在很明显，是特定的营养素而不是卡路里介导了寿命的延长。几何框架还揭示了繁殖和寿命之间权衡的营养基础。这与跟踪氮、碳和必需氨基酸在卵子与繁殖之间分配的稳定同位素分析相辅相成。这些研究表明，通过一种将资源从繁殖重新分配到体细胞维持的机制来解释 DR 如何延长寿命是不可能的。尽管从原则上讲很有前景，但 DR 机制的遗传分析取得的成功有限。为了取得成效，研究必须在适当的浓度下包含足够的饮食。在回顾最佳数据时，迄今为止，几乎没有证据表明任何基因是 DR 延长果蝇寿命所必需的，包括胰岛素信号或 4eBP。在未来的果蝇研究中，对 DR 所需基因进行强有力的分析应该是优先事项，这可以通过在几何框架的背景下考虑突变体的影响来使其最稳健。
