Epigenetic regulation of extreme longevity differences in ant castes

蚂蚁种姓极端长寿差异的表观遗传调控

• 批准号: 10708181
• 负责人: SHELLEY L BERGER
• 金额: $ 47.06万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708181
• 关键词: Age; Aging; Animal Model; Ants; Behavior; Binding; Biological Models; Castes; Chromatin; Complex; Disparity; Ectopic Expression; Epigenetic Process; Etiology; Excision; Exhibits; Family; Female; Food; Funding; Genetic; Genetic Transcription; Genome; Genomics; Goals; HSF1; Heart; Heat Stress Disorders; Heat shock factor; Heat-Shock Response; Heat-Shock Transcription Factor 2; Histone Acetylation; Individual; Insecta; Investigation; Knowledge; Life; Link; Longevity; Mammals; Messenger RNA; MicroRNAs; Minor; Modeling; Pathway interactions; Physiological; Proteins; Proteomics; Regulation; Reproduction; Research; Role; Social Behavior; Soldier; Sterility; Stress; Testing; Translating; Up-Regulation; epigenetic regulation; epigenomics; histone methylation; human model; mortality; non-genetic; novel; programs; protein structure; reproductive; transcription factor

ABSTRACT Ants exhibit highly evolved eusocial behaviors including stark division of labor among female castes, where the queen carries out all reproduction and worker castes forage for food and defend the colony. Interestingly, and of great relevance to aging research, sterile workers are shorter-lived, with variable lifespans between distinct castes. Reproductive queens are long-lived, with lifespans differing three to ten-fold between queen and worker. Remarkably, the genomes of the sterile and reproductive castes are nearly identical, and thus differences in lifespan and behavior arise from non-genetic mechanisms. We investigate two species of ants, each with advantages for study of mechanisms linking aging with complex social behavior. In Harpegnathos saltator, loss or removal of the queen leads to altered behavior in the workers, with antennal dueling and eventual ascendance of workers to reproductive status. From a longevity perspective, the induced reproductive caste exhibits four-fold longer lifespan, thus providing a simple experimental switch to uncover important causality underlying aging. In Camponotus floridanus, there are two distinct worker castes, forager and soldier, with the soldier exhibiting a two-fold longer lifespan than the forager. These behaviors are programmed early in life, but exhibit plasticity during aging. Intriguingly, these castes can be experimentally reprogrammed from soldier-to-forager, thus providing a second paradigm to study the relationship of behavior to aging. Our overall premise is that genomic, epigenomic, and proteomic regulation—all hallmark foundational causes of aging—are at the heart of caste-differentiated lifespan disparities and relationship to caste behavior. We thus propose to utilize ants to investigate the epigenetic and physiological basis of the dramatic lifespan differences between reproductive and distinct worker castes. In H. saltator we have evidence in the long-lived reproductive caste for two mechanisms extending lifepan. First, we detect increased expression of a unique HSF (Heat Shock Factor) providing proteomic protection and longer lifespan via upregulation of the Heat Shock Response transcriptional pathway. Second, we find increased expression of a unique Ago2 (Arogonaut) that binds miRNAs that specifically target for destruction certain mRNAs that lower lifespan in short-lived workers. In C. floridanus we find that distinct chromatin-based epigenetic mechanisms are central to foraging, which is an age-linked behavior, and we can manipulate these pathways to reprogram soldier caste to forage. In the proposed research we will investigate these causal mechanisms, and then manipulate lifespan with a combination of genetic and epigenetic approaches to promote these mechanisms. The ant model system provides an exceptional opportunity to integrate social behavior with aging, and to uncover key epigenetic processes underlying universal aging pathways. Results from the research will provide fundamental knowledge about control of lifespan that can be translated to more sophisticated mammals.

抽象的 蚂蚁表现出高度进化的社会行为，包括女性种姓之间严格的劳动分工，其中 女王负责所有繁殖工作，工蚁则寻找食物并保卫殖民地。 与衰老研究密切相关的是，不育工人的寿命较短，不同的工人之间的寿命存在差异。 具有生殖能力的女王寿命很长，女王和女王之间的寿命相差三到十倍。 值得注意的是，不育种姓和繁殖种姓的基因组几乎相同，因此。 寿命和行为的差异源于非遗传机制，我们研究了两种蚂蚁， 每种方法都有利于研究衰老与复杂社会行为之间的联系机制。 跳跃者，蜂王的损失或移除会导致工蜂的行为改变，包括触角决斗和 从长寿的角度来看，诱导生殖是工人最终获得生殖地位的过程。 种姓的寿命延长四倍，从而提供了一个简单的实验转换来发现重要的 佛罗里达弓背蚁有两个不同的工种：采集者和工蚁。 士兵的寿命是采集者的两倍，这些行为是经过编程的。 有趣的是，这些种姓可以通过实验重新编程。 从士兵到采集者，从而提供了研究行为与衰老关系的第二种范式。 总体前提是基因组、表观基因组和蛋白质组调控——所有标志性的根本原因 老龄化是种姓差异寿命差异以及与种姓行为关系的核心。 因此，我们建议利用蚂蚁来研究戏剧性事件的表观遗传和生理基础。 在 H. saltator 中，我们有证据表明生殖种姓和不同工人种姓之间的寿命差异。 长寿生殖种姓有两种延长寿命的机制：首先，我们检测到a的表达增加。 独特的 HSF（热休克因子）通过上调提供蛋白质组保护并延长寿命 其次，我们发现独特的 Ago2 表达增加。 (Arogonaut) 结合 miRNA，专门针对破坏某些降低寿命的 mRNA 在短命工蚁中，我们发现基于染色质的独特表观遗传机制是其核心。 觅食，这是一种与年龄相关的行为，我们可以操纵这些途径来重新编程士兵种姓 在拟议的研究中，我们将研究这些因果机制，然后操纵寿命。 结合遗传和表观遗传方法来促进这些机制。 系统提供了一个绝佳的机会将社会行为与衰老相结合，并发现关键的 研究结果将提供基础的普遍衰老途径的表观遗传过程。 有关控制寿命的知识可以转化为更复杂的哺乳动物。