The Physiological and Metabolic Basis of the Fecundity/Longevity Trade-Off in Drosophila

在许多生物体中，减少繁殖可以延长寿命。相反，寿命的延长往往伴随着繁殖的减少。有趣的是，在没有营养不良（饮食限制）的情况下减少食物摄入量也会延长寿命，同时减少生殖。这些观察结果表明，长寿生殖权衡可能代表了一个充满活力的资源分配权衡，即食物限制可能会转移资源从生殖，使它们可用于体细胞的维护和生存。然而，在繁殖力和代谢储存之间的能量分配的权衡是不定量的精确和饮食限制可以增加寿命的性腺切除蠕虫（秀丽隐杆线虫）和不育苍蝇（果蝇），这是在与资源分配模型的发现。与C.缺乏整个生殖腺的秀丽线虫、仅缺乏生殖细胞的蠕虫（和苍蝇）是长寿的，并且饮食限制不能进一步延长这些个体的寿命，这表明来自生殖系的信号可能与体细胞生殖腺的信号相反，以调节衰老。因此，虽然目前的知识表明，营养代谢，生殖和衰老代表相互关联的调节轴，生殖和长寿之间的权衡的实际机制仍然在很大程度上是未知的。这里提出的研究的主要目标是获得新的见解生殖寿命权衡，在生命史进化和衰老生物学的中心问题的机制。具体来说，我们试图测试的假设，生殖和营养调节轴收敛到相同的机制，影响衰老。我们建议通过使用果蝇模型来研究这一假设，以检查饮食限制对（1）正常繁殖和不育果蝇（有和没有增殖生殖系）的寿命以及（2）生殖和体细胞组织中基因表达谱的影响。

In many organisms curtailed reproduction increases lifespan. Conversely, extended lifespan is often accompanied by reduced reproduction. Interestingly, decreased food intake without malnourishment (dietary restriction) also promotes lifespan while concomitantly reducing reproduction. These observations suggest that the longevity-reproduction trade-off might represent an energetic resource allocation trade-off whereby food limitation might divert resources away from reproduction and make them available for somatic maintenance and survival. However, the tradeoff in energy allocation between fecundity and metabolic storage is not quantitative exact and dietary restriction can increase lifespan in gonadectomized worms (Caenorhabditis elegans) and sterile flies (Drosophila melanogaster), findings which are at odds with the resource allocation model. In contrast to C. elegans that lack the entire gonad, worms (and flies) that lack germ cells only are long-lived and dietary restriction cannot further extend longevity in these individuals, suggesting that signals from the germline may oppose those of the somatic gonad to regulate aging. Therefore, although current knowledge indicates that nutrient metabolism, reproduction and aging represent interconnected regulatory axes, the actual mechanisms underlying the trade-off between reproduction and longevity remain largely unknown. The main goal of the research proposed here is to gain novel insights into the mechanisms underlying the reproduction-longevity trade-off, a central problem in life history evolution and in the biology of aging. Specifically, we seek to test the hypothesis that the reproductive and nutritional regulatory axes converge onto the same mechanisms that affect aging. We propose to investigate this hypothesis by using the fly model Drosophila melanogaster to examine the consequences of dietary restriction on (1) longevity in normally reproducing and sterile flies (with and without proliferating germline) and on (2) gene expression profiles in reproductive and somatic tissues.