Characterization of Aging in Sea Urchin Species with Different Life Spans

描述（由申请人提供）：我们目前对衰老生物学的理解主要是对短期实验室模型（如酵母、蠕虫、苍蝇和小鼠）的研究结果。有一类动物可能揭示出一些对抗衰老破坏性过程的新策略，它们在整个生命周期中持续生长和繁殖，衰老缓慢或根本不衰老。虽然已经描述了几种可以忽略不计的衰老动物，但其中许多动物对实验室研究提出了实际，技术和伦理挑战。作为一个例外，海胆提出了一个独特的和易于处理的模型，用于研究衰老和可忽略的衰老。海胆是一种完善的实验室模型，与其他无脊椎动物模型（即蠕虫和苍蝇）相比，它们与人类的关系更密切，并且有大量的细胞和分子工具可用于它们的研究。不同种类的海胆有着截然不同的自然寿命，有些种类的海胆寿命极长，衰老可以忽略不计。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，并了解长寿物种不衰老的机制。初步的基因组学数据有助于形成我们的核心假设，即寿命较长的物种具有更大的组织再生和修复能力，寿命最长的物种具有减轻细胞氧化损伤的独特能力。本提案的目的是通过检查具有不同寿命的海胆物种组织中的细胞损伤和再生指标来检验这一假设; Strongylocentrotus franciscanus（寿命>100年）、Strongylocentrotus purpuratus（寿命50年）和Lytechinus variegatus（寿命4年）。再生指标将通过研究跨越每个物种生命周期的不同年龄动物组织中的细胞增殖和细胞凋亡来评估。将通过测量细胞损伤的总体水平来评估修复或减轻损伤的能力，所述细胞损伤例如来自跨越每个物种的寿命的不同年龄的动物的组织中的脂褐素、8-羟基脱氧鸟苷、蛋白质羰基和丙二醛。这些长，中，短寿命的物种之间的比较将有助于确定关键的细胞和分子途径，确定其不同的生活史，并将揭示机制，可以忽略不计的长寿物种的衰老。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率较慢的机制和对衰老表型的不寻常抗性的机制。由于海胆与人类的关系比其他无脊椎动物模型更密切，这些模型为衰老过程提供了重要的见解，毫无疑问，从这些研究中获得的信息将直接与人类生物学相关，并可能最终导致预防或治疗与年龄有关的疾病的新途径。

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.