Monogonont Rotifers as a Model to Investigate the Biology of Aging

单角轮虫作为研究衰老生物学的模型

• 批准号: 7983063
• 负责人: Terry W Snell
• 金额: $ 29.71万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983063
• 关键词: Accounting; Age; Aging; Aging-Related Process; Alleles; Animal Model; Animals; Arthropods; Asexual Reproduction; Back; Biological Models; Biology of Aging; Boxing; Caenorhabditis elegans; Chromosomes, Human, Pair 5; Cnidaria; Complex; DNA; DNA Damage; Detection; Development; Diabetes Mellitus; Diapause; Diet; Gene Expression; Generations; Genes; Genetic; Genetic Transcription; Genome; Goals; Growth; Haploidy; Homeostasis; Homologous Gene; Human; Inbreeding; Institutes; Intervention; Invertebrates; Lead; Lipids; Longevity; Mental Depression; Metabolic Diseases; Metabolism; Mitogens; Modeling; Molecular; Nematoda; Obesity; Oxidative Stress; Pathway interactions; Phylogenetic Analysis; Positioning Attribute; Process; Production; Proteins; Protocols documentation; RNA Interference; Recording of previous events; Research; Role; Rotifera; Signal Pathway; Signal Transduction; Stress; Temperature; Time; Tissues; Work; Wound Healing; age effect; age related; asexual; cellular longevity; detection of nutrient; dietary restriction; egg; fly; genetic resource; genome sequencing; inhibitor/antagonist; life history; longevity gene; male; mortality; novel strategies; oxidative damage; public health relevance; reproductive; research study; response; senescence; theories; tissue regeneration; tool; trait

DESCRIPTION (provided by applicant): Rotifers are a potentially valuable new model to investigate the mechanisms of aging, as well as homeostasis and tissue regeneration, the effects of reproductive mode (asexual versus sexual) on longevity, and the cellular and molecular processes of senescence. Moreover, as basal metazoans, rotifers may share more genes with humans than Ecdyzoan animal models like C. elegans and D. melanogaster. In the proposed work we identify new genes associated with rotifer aging and search for their homologs in humans. Monogonont rotifers have specific features that make them an attractive models for aging studies, including: 1) a history of aging related research extending back nearly a century; 2) asexual propagation of clonal cultures, so that experiments can take place in the same genetic background, without the potential inbreeding depression imposed on isogenic lines; 3) sexual and asexual reproduction in the same genetic background; 4) haploid males, allowing direct expression of alleles and simplifying crosses in the absence of complex marker chromosomes; 5) production of highly stable diapausing eggs; 5) many closely related strains and species that differ in life history traits; and 6) A well developed tool box of genetic resources including partially sequenced genomes and transcriptomes, and a working RNAi protocol. In the proposed work, we determine the effects on aging and longevity of dietary restriction, oxidative stress, and elevated temperature in five closely related strains of the Brachionus plicatilis species complex. The effect of sexual and asexual reproduction on aging also is investigated and correlated with cumulative oxidative damage to proteins, lipids, and DNA. We also identify genes involved in aging and longevity by examining the transcription profiles of rotifers of different ages under different dietary, reproductive, and stress conditions, and confirm the activity of specific genes by RNAi and qtPCR. The role of diapause in aging also is investigated by examining the mechanisms by which diapause in Brachionus alters tissue homeostasis, suspends metabolism during dormancy, and stimulates tissue repair following dormancy. The degree of aging observed in rotifers that have been kept in a dormant state for up to 25 years also is examined. PUBLIC HEALTH RELEVANCE: Rotifers are a valuable new invertebrate model to investigate the mechanisms of aging, including homeostasis and tissue regeneration, the effects of reproductive mode (asexual versus sexual) and diapause on longevity, and the cellular and molecular processes of senescence. Because of their phylogenetic relationship to humans and other animals, they can be useful in the identification of genes that regulate aging. Identifying evolutionarily conserved genes in Ecdysozoan and spiralian phyla that regulate organismal aging could provide attractive targets for pharmacological intervention in mammalian aging. Molecular understanding of how dietary restriction extends lifespan will have direct implications for new approaches to treat metabolic diseases like diabetes and obesity.

描述（由申请人提供）：转火是一种潜在的有价值的新模型，用于研究衰老机制，体内平衡和组织再生的机制，生殖模式（无性与性）对寿命的影响以及寿命的细胞和分子过程。此外，作为基底后生动物，旋风可能与ecdyzoan动物模型（如秀丽隐杆线虫和D. melanogaster）相比，与人类共享基因更多。 在拟议的工作中，我们确定了与旋转器衰老相关的新基因，并在人类中寻找其同源物。 一单子旋转器具有特定的特征，使它们成为衰老研究的有吸引力的模型，包括：1）衰老相关研究的历史，延伸了近一个世纪； 2）克隆培养物的无性传播，以便可以在相同的遗传背景下进行实验，而不会在等源性线上施加近亲繁殖抑郁。 3）在相同的遗传背景中的性和无性繁殖； 4）单倍体雄性，在没有复杂的标记染色体的情况下，可以直接表达等位基因并简化杂交； 5）产生高度稳定的育鸡蛋； 5）许多与人生历史特征不同的密切相关的菌株和物种； 6）一个开发了良好的遗传资源工具盒，包括部分测序的基因组和转录组以及工作RNAi方案。 在拟议的工作中，我们确定了饮食限制，氧化应激和温度升高的衰老和寿命升高的五个密切相关菌株的影响。 还研究了性和无性繁殖对衰老的影响，并与对蛋白质，脂质和DNA的累积氧化损伤相关。 我们还通过检查不同饮食，生殖和压力条件下不同年龄的旋转膜的转录谱，并确认RNAi和QTPCR的特定基因的活性，从而鉴定出与衰老和寿命有关的基因。 还可以通过检查乳杆菌改变组织稳态，暂停休眠期间的新陈代谢并刺激休眠后的组织修复的机制来研究肿瘤在衰老中的作用。还检查了在处于休眠状态长达25年的轮状膜中观察到的衰老程度。 公共卫生相关性：旋转器是一个有价值的新无脊椎动物模型，用于研究衰老机制，包括体内平衡和组织再生，生殖模式（无性与性）对寿命的影响以及寿命以及寿命的细胞和分子过程。由于它们与人类和其他动物的系统发育关系，它们可以在调节衰老的基因的鉴定中有用。确定调节有机体衰老的Ecdysozoan和螺旋形门中进化保守的基因可以为哺乳动物衰老的药理干预提供有吸引力的靶标。分子对饮食限制如何延长寿命的理解将对治疗诸如糖尿病和肥胖症等新陈代谢疾病的新方法具有直接影响。