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

饮食限制对性别特异性衰老的新无脊椎动物模型的影响

• 批准号: 10629330
• 负责人: Suzanne Edmands
• 金额: $ 8.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629330
• 关键词: 8-hydroxy-2' -deoxyguanosine; Address; Age; Aging; Animals; Backcrossings; Biogenesis; Biological Assay; Copepoda; DNA Damage; Data; Diet; Dietary Intervention; Drosophila genus; Enzymes; Family; Female; Food; Freezing; Future; Gene Expression; Genes; Guanine; Haplotypes; Health; Human; Hybrids; Immunosorbents; Individual; Intervention; Invertebrates; Life; Life Extension; Link; Longevity; Measures; Mitochondria; Mitochondrial DNA; Modeling; Mus; Nematoda; Nuclear; Organism; Oxidative Phosphorylation; Oxidative Stress; Pattern; Pilot Projects; Ploidies; Population; Reporting; Role; Series; Sex Chromosomes; Sex Differences; System; Testing; Work; Yeasts; dietary; dietary restriction; food restriction; food standard; improved; male; oxidative DNA damage; response; sex; stress tolerance; success; survivorship

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.

项目摘要 饮食限制（DR）已被证明会在广泛的生物中增加寿命 包括酵母，线虫，水果粉，老鼠和人类。但是，对 DR对衰老的影响如何不同。此外，虽然线粒体功能是 我们对饮食对寿命的影响的理解，即替代线粒体的影响 仅在有限的 分类单元的数量。拟议的项目使用新的无脊椎动物解决了这些问题 衰老模型，Copepod Tigriopus加利福尼亚。该物种非常适合评估 线粒体和线核对衰老的影响，因为可行和肥沃的杂种很容易 在人群之间的十字架中产生，线粒体DNA差异很大 （mtDNA）。此外，由于该物种缺乏性染色体，因此特定性线粒体 效果与性染色体的作用不混淆。重要的是，物种显示 女性养育可能会影响DR成功的特征的戏剧性性别差异 在寿命较​​短的控制条件下，较高的应激耐受性，更高的mtDNA含量， 较低的8-OH-DG DNA损伤，与氧化磷酸化有关的基因的较低表达 以及参与线粒体生物发生的基因的较高表达。因为DR的影响 在该物种中从未研究过衰老，该试验研究首先测试了 一系列针对特定性别寿命的限制食品口粮。而且因为博士的成功 随着线型的不同，将在将三种不同的线粒体上进行测定 核背景。作为对DR功能后果的初步测试，线条将是 分析两个性别的线粒体拷贝数和DNA损伤。通过提供 关于加州综合综合饮食限制的响应的基础数据，该项目将铺路 旨在理解性别特定机制的该物种的未来工作的方式 线粒体对DR的反应。