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也能延长寿命，同时也会减少繁殖。这些观察结果表明，长寿与繁殖之间的权衡可能代表了一种能量资源分配的权衡，即食物限制可能会将资源从繁殖中转移出来，使其可用于身体的维持和生存。然而，繁殖力和代谢储存之间能量分配的权衡并不是定量精确的，并且限制饮食可以延长性腺去化蠕虫（秀丽隐杆线虫）和不育果蝇（黑腹果蝇）的寿命，这与资源分配模型不一致。与缺乏整个性腺的秀丽隐杆线虫不同，仅缺乏生殖细胞的蠕虫（和苍蝇）寿命较长，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性腺的信号相反，以调节衰老。因此，尽管目前的知识表明营养代谢、繁殖和衰老代表着相互关联的调节轴，但繁殖和长寿之间权衡的实际机制在很大程度上仍然未知。这项研究的主要目标是对生殖与寿命权衡的机制有新的认识，这是生命史进化和衰老生物学中的一个核心问题。具体来说，我们试图测试生殖和营养调节轴汇聚到影响衰老的相同机制的假设。我们拟通过果蝇模型黑腹果蝇（Drosophila melanogaster）来研究饮食限制对(1)正常生殖和不育果蝇（有或没有生殖系）寿命的影响，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.