Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Edinburgh Genomics, Roslin Institute, University of Edinburgh, Edinburgh, UK.
Aging Cell. 2019 Feb;18(1):e12868. doi: 10.1111/acel.12868. Epub 2018 Nov 20.
Dietary restriction (DR) is one of the main experimental paradigms to investigate the mechanisms that determine lifespan and aging. Yet, the exact nutritional parameters responsible for DR remain unclear. Recently, the advent of the geometric framework of nutrition (GF) has refocussed interest from calories to dietary macronutrients. However, GF experiments focus on invertebrates, with the importance of macronutrients in vertebrates still widely debated. This has led to the suggestion of a fundamental difference in the mode of action of DR between vertebrates and invertebrates, questioning the suggestion of an evolutionarily conserved mechanism. The use of dietary dilution rather than restriction in GF studies makes comparison with traditional DR studies difficult. Here, using a novel nonmodel vertebrate system (the stickleback fish, Gasterosteus aculeatus), we test the effect of macronutrient versus calorie intake on key fitness-related traits, both using the GF and avoiding dietary dilution. We find that the intake of macronutrients rather than calories determines both mortality risk and reproduction. Male mortality risk was lowest on intermediate lipid intakes, and female risk was generally reduced by low protein intakes. The effect of macronutrient intake on reproduction was similar between the sexes, with high protein intakes maximizing reproduction. Our results provide, to our knowledge, the first evidence that macronutrient, not caloric, intake predicts changes in mortality and reproduction in the absence of dietary dilution. This supports the suggestion of evolutionary conservation in the effect of diet on lifespan, but via variation in macronutrient intake rather than calories.
饮食限制（DR）是研究决定寿命和衰老的机制的主要实验范例之一。然而，负责 DR 的确切营养参数仍不清楚。最近，营养的几何框架（GF）的出现重新引起了人们对卡路里到膳食宏量营养素的兴趣。然而，GF 实验主要集中在无脊椎动物上，而脊椎动物中宏量营养素的重要性仍在广泛争论。这导致了 DR 在脊椎动物和无脊椎动物之间作用模式的根本差异的建议，质疑了进化保守机制的建议。GF 研究中使用饮食稀释而不是限制使得与传统 DR 研究进行比较变得困难。在这里，我们使用一种新型非模型脊椎动物系统（棘鱼，Gasterosteus aculeatus），通过避免饮食稀释，使用 GF 测试宏量营养素与卡路里摄入量对关键与健康相关特征的影响。我们发现，宏量营养素的摄入而不是卡路里决定了死亡率和繁殖风险。雄性死亡率风险在中间脂质摄入时最低，而雌性风险通常因低蛋白质摄入而降低。宏量营养素摄入对繁殖的影响在两性之间相似，高蛋白摄入使繁殖最大化。我们的研究结果提供了，据我们所知，第一个证据表明，在没有饮食稀释的情况下，宏量营养素而不是卡路里的摄入预测死亡率和繁殖的变化。这支持了饮食对寿命的影响在进化上保守的建议，但通过宏量营养素摄入的变化而不是卡路里。
