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Characterization of Aging in Sea Urchin Species with Different Life Spans

不同寿命海胆物种的衰老特征

基本信息

批准号：
8337830
负责人：
Andrea Bodnar
金额：
$ 16.49万
依托单位：
BERMUDA INSTITUTE OF OCEAN SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8337830
关键词：
8-hydroxy-2&apos -deoxyguanosine Age Aging Aging-Related Process Animal Model Animals Apoptosis Biochemical Biochemistry Bioinformatics Biological Process Biology of Aging Caenorhabditis elegans Cell Proliferation Cell physiology Cells Data Disease Esophagus Ethics Exhibits Foundations Future Gene Expression Genetic Genomics Goals Health Human Human Biology Invertebrates Investigation Laboratories Laboratory Study Lead Learning Life Life Expectancy Lipofuscin Longevity Lytechinus variegatus Malondialdehyde Measures Modeling Molecular Mus Muscle Natural regeneration Pathway interactions Pattern Phenotype Physiological Physiological Processes Physiology Prevention Proteins Red Sea Research Resistance Sea Urchins Strongylocentrotus Strongylocentrotus purpuratus Structure of radial nerve Study models Testing Time Tissues Uncertainty Variant Yeasts age related animal tissue base fly insight life history mortality novel strategies oxidative damage repaired reproductive research study resistance mechanism senescence tissue regeneration tissue repair tool

项目摘要

DESCRIPTION (provided by applicant): Our current understanding of the biology of aging is largely the result of studies in short-lived laboratory models such as yeast, worms, flies and mice. One class of animals that may reveal some novel strategies against the destructive process of aging are those that continue to grow and reproduce throughout their life spans and age either slowly or not at all. Although several animals with negligible aging have been described many of them present practical, technical and ethical challenges for laboratory studies. As an exception, sea urchins present a unique and tractable model for the study of aging and negligible senescence. Sea urchins are a well established laboratory model that are more closely related to humans than other invertebrate models (i.e. worms and flies) and there are a large number of cellular and molecular tools available for their study. Different species of sea urchins have very different natural life spans and there are some species which display extreme longevity and negligible senescence. The long-term goals of this project are to define the molecular, cellular and physiological basis for differences in longevity between species of sea urchins and to understand the mechanisms underlying the absence of aging in the long-lived species. Preliminary genomics data have helped form our central hypothesis in which longer lived species have a greater capacity for tissue regeneration and repair and the longest lived species has a unique ability to mitigate cellular oxidative damage. The objectives of this proposal are to test this hypothesis by examining indicators of cellular damage and regeneration in the tissues of sea urchins species with different life spans; Strongylocentrotus franciscanus (life span >100 years), Strongylocentrotus purpuratus (life span 50 years) and Lytechinus variegatus (life span 4 years). Indicators of regeneration will be assessed by investigating cell proliferation and apoptosis in tissues from animals of different ages spanning the life span of each species. The capacity for repair or mitigation of damage will be assessed by measuring overall levels of cellular damage such as lipofuscin, 8-hydroxydeoxyguanosine, protein carbonyls and malondialdehyde in tissues from animals of different ages spanning the life span of each species. Comparisons between these long-, intermediate- and short-lived species will facilitate the identification of critical cellular and molecular pathways that determine their different life histories and will uncover mechanisms of negligible senescence in the long-lived species. The use of sea urchins as models for aging provides a novel approach to uncover mechanisms leading to slower rates of aging and mechanisms for unusual resistance to senescent phenotypes. Since sea urchins are more closely related to humans than are other invertebrate models that have provided significant insight into the process of aging, there is little doubt that the information gained from these studies will be directly relevant to human biology and may ultimately lead to new avenues for prevention or treatment of age-related diseases.

描述(由申请人提供)：我们目前对衰老生物学的了解主要是通过对酵母、蠕虫、苍蝇和老鼠等短期实验室模型的研究得出的。一类动物可能会揭示一些新的策略来对抗破坏性的衰老过程，这些动物在整个生命周期中继续生长和繁殖，或者缓慢或根本不衰老。尽管已经描述了几种衰老程度可以忽略不计的动物，但其中许多动物对实验室研究提出了实际、技术和伦理方面的挑战。作为一个例外，海胆为研究衰老和可忽略的衰老提供了一个独特和易处理的模型。海胆是一个成熟的实验室模型，与其他无脊椎动物模型(如蠕虫和苍蝇)相比，它们与人类的关系更密切，而且有大量的细胞和分子工具可用于研究它们。不同种类的海胆的自然寿命差异很大，有些物种表现出极长的寿命和微不足道的衰老。该项目的长期目标是确定海胆物种之间寿命差异的分子、细胞和生理基础，并了解长寿物种中没有衰老的潜在机制。初步的基因组学数据帮助形成了我们的核心假设，即寿命较长的物种具有更大的组织再生和修复能力，而寿命最长的物种具有减轻细胞氧化损伤的独特能力。这项建议的目的是通过检查不同寿命的海胆物种、法国海胆(寿命100岁)、紫球海胆(寿命50岁)和变色海胆(寿命4年)组织中的细胞损伤和再生指标来检验这一假设。再生指标将通过调查不同年龄动物组织中的细胞增殖和凋亡来评估，这些组织跨越每个物种的生命周期。修复或减轻损伤的能力将通过测量不同年龄动物组织中脂褐素、8-羟基脱氧鸟苷、蛋白质羰基和丙二醛等细胞损伤的总体水平来评估，这些组织跨越每个物种的生命周期。对这些长寿、中寿和短寿物种进行比较，将有助于识别决定它们不同生活史的关键细胞和分子途径，并揭示这些长寿物种可以忽略不计的衰老机制。使用海胆作为衰老模型提供了一种新的方法来揭示导致衰老速度较慢的机制以及对衰老表型的异常抵抗机制。由于海胆与人类的关系比其他无脊椎动物模型更接近人类，这些无脊椎动物模型对衰老过程提供了重要的见解，因此毫无疑问，从这些研究中获得的信息将与人类生物学直接相关，并最终可能导致预防或治疗与年龄相关的疾病的新途径。