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: 10431556
• 负责人: Suzanne Edmands
• 金额: $ 7.79万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10431556
• 关键词: 8-hydroxy-2' -deoxyguanosine; Address; Age; Aging; Animals; Backcrossings; Biogenesis; Biological Assay; Copepoda; DNA Damage; DNA copy number; Data; Diet; Dietary Intervention; Enzyme-Linked Immunosorbent Assay; Enzymes; Family; Female; Food; Foundations; 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; Oxides; Pattern; Pilot Projects; Ploidies; Population; Reporting; Role; Series; Sex Chromosomes; Sex Differences; System; Testing; Work; Yeasts; base; dietary; dietary restriction; food standard; 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）已被证明可以延长多种生物体的寿命 包括酵母、线虫、果蝇、小鼠和人类。然而，人们对它知之甚少。 DR对衰老的影响如何在性别之间存在差异。此外，虽然线粒体功能是核心， 我们对饮食对寿命的影响的理解， 单倍型（有丝分裂型）对DR干预成功的影响仅在有限的研究中进行了探讨。 taxa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 衰老的模型，桡足类加州虎足虫。这个物种非常适合评估 线粒体和线粒体对衰老的影响，因为可行的和可育的杂种很容易 在线粒体DNA差异极大的种群间杂交时产生 （mtDNA）。此外，由于该物种缺乏性染色体， 这些效应不会与性染色体的效应混淆。重要的是，该物种表明， 在可能影响DR成功的特征方面存在显著的性别差异， 在对照条件下具有较短的寿命，较高的胁迫耐受性，较高的mtDNA含量， 降低8-OH-dG DNA损伤，降低参与氧化磷酸化的基因表达 以及参与线粒体生物发生的基因的更高表达。因为DR对 衰老从来没有在这个物种中进行过研究，这项初步研究首先测试了 一系列限制性食物配给对性别特定寿命的影响。由于DR的成功可能 随着有丝分裂型的不同，将对放置在相同细胞上的三种不同的有丝分裂型进行测定。 核背景作为对DR功能结果的初步测试， 测定两种性别的线粒体拷贝数和DNA损伤。通过提供 T.加州饮食限制，该项目将铺平道路 未来对这一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