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.

项目概要 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，人们对此知之甚少 DR 对衰老的影响在性别之间有何不同。此外，虽然线粒体功能对于 我们对饮食对寿命影响的理解，替代线粒体的影响 仅在有限的范围内探索了与 DR 干预成功相关的单倍型（有丝分裂型） 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 衰老模型，桡足类 Tigriopus californicus。该物种非常适合评估 线粒体和线粒体核对衰老的影响，因为可存活且可育的杂交体很容易 线粒体 DNA 差异巨大的群体之间杂交产生的 （线粒体DNA）。此外，由于该物种缺乏性染色体，性别特异性线粒体 效应不与性染色体的效应相混淆。重要的是，该物种表明 特征上的巨大性别差异可能会影响 DR 的成功，其中女性长大 在寿命较​​短、抗逆性较高、mtDNA含量较高的对照条件下， 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 的影响 从未在该物种中研究过衰老，这项试点研究首先测试了 对特定性别寿命的一系列限制食物配给。而且因为 DR 的成功可能 随线粒体型的不同而变化，将对置于同一细胞上的三种不同的线粒体型进行测定 核背景。作为 DR 功能后果的初步测试，线路将被 测定了两性的线粒体拷贝数和 DNA 损伤。通过提供 关于加州 T. californicus 对饮食限制的反应的基础数据，该项目将为 该物种未来的工作方式旨在了解特定性别的机制 线粒体对 DR 的反应。