Effects of dietary restriction in a new invertebrate model for sex-specific aging

项目摘要 饮食限制(DR)已被证明可以延长多种生物体的寿命 包括酵母、线虫、果蝇、老鼠和人类。然而，人们对此知之甚少。 DR对衰老的影响在不同性别之间有何不同。此外，虽然线粒体功能是 我们对饮食对寿命的影响、替代线粒体的影响的理解 单倍型(有丝分裂型)对DR干预成功的探讨有限 分类群的数量。拟议的项目使用一种新的无脊椎动物来解决这些问题 用于衰老的模式，尺足类老虎。本种非常适合于评估 线粒体和有丝分裂核对衰老的影响，因为活的和有生育能力的杂交很容易 产生于线粒体DNA差异极大的群体之间的杂交 (MtDNA)。此外，由于该物种缺乏性染色体，性别特有的线粒体 这种影响并不与性染色体的影响相混淆。重要的是，这个物种表明 在可能影响DR成功的特征上存在显著的性别差异，女性有所提高 在寿命较短、抗逆性较高、mtDNA含量较高的对照条件下， 减少8-OH-DG DNA损伤，降低氧化磷酸化相关基因的表达 线粒体生物发生相关基因的高表达。因为DR对 衰老在这个物种中从未被研究过，这项初步研究首先测试了一种 一系列限制特定性别寿命的食品配给。也是因为梅博士的成功 根据有丝分裂型的不同，将对放置在同一细胞上的三种不同的有丝分裂型进行分析 核背景。作为DR功能后果的初步测试，LINES将 检测男女的线粒体拷贝数和DNA损伤。通过提供 本项目将为研究加州管圆线虫对饲料限制的反应提供基础数据 未来对该物种的研究旨在了解性别特异性的机制 线粒体对DR的反应

Project Summary Dietary restriction (DR) has been shown to increase lifespan in a wide range of organisms including yeast, nematodes, fruitflies, mice and humans. However, fairly little is known about how DR effects on aging differ between sexes. Further, while mitochondrial function is central to our understanding of dietary effects on lifespan, the impact of alternative mitochondrial haplotypes (mitotypes) on the success of DR intervention have been explored in only a limited number of taxa. The proposed project addresses these questions using a new invertebrate model for aging, the copepod Tigriopus californicus. This species is well suited to assessing mitochondrial and mitonuclear impacts on aging, because viable and fertile hybrids are easily produced in crosses between populations with tremendously divergent mitochondrial DNA (mtDNA). Further, because the species lacks sex chromosomes, sex specific mitochondrial effects are not confounded with the effects of sex chromosomes. Importantly, the species shows dramatic sex differences in features that may impact the success of DR, with females raised under control conditions having shorter lifespan, higher stress tolerance, higher mtDNA content, lower 8-OH-dG DNA damage, lower expression of genes involved in oxidative phosphorylation and higher expression of genes involved in mitochondrial biogenesis. Because effects of DR on aging have never been investigated in this species, this pilot study first tests the effects of a series of restricted food rations on sex-specific lifespan. And because the success of DR may vary with mitotype, assays will be done on three different mitotypes placed onto the same nuclear background. As a preliminary test of the functional consequences of DR, lines will be assayed for mitochondrial copy number and DNA damage in both sexes. By providing foundational data on the response of T. californicus to dietary restriction, this project will pave the way for future work on this species aimed at understanding mechanisms of sex-specific mitochondrial response to DR.