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

基本信息

批准号：
8728090
负责人：
Terry W Snell
金额：
$ 29.54万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8728090
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 Chromosome Markers Cnidaria Complex DNA DNA Damage Detection Development Diabetes Mellitus Diapause Diet Gene Expression Gene Expression Profile 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 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 reproductive research study response senescence theories tissue regeneration tissue repair tool trait

项目摘要

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.

描述（由申请人提供）：轮虫是一种潜在有价值的新模型，可用于研究衰老机制、体内平衡和组织再生、生殖模式（无性与有性）对寿命的影响以及衰老的细胞和分子过程。此外，作为基础后生动物，轮虫可能比线虫和黑腹果蝇等蜕皮动物模型与人类共享更多基因。在拟议的工作中，我们鉴定了与轮虫衰老相关的新基因，并在人类中寻找它们的同源物。单角轮虫具有使其成为衰老研究有吸引力的模型的特定特征，包括：1）衰老相关研究的历史可以追溯到近一个世纪； 2) 克隆培养物的无性繁殖，以便实验可以在相同的遗传背景下进行，而不会对同基因系造成潜在的近交抑制； 3）相同遗传背景下的有性和无性生殖； 4) 单倍体雄性，允许直接表达等位基因并在没有复杂标记染色体的情况下简化杂交； 5）生产高度稳定的滞育蛋； 5）许多密切相关的菌株和物种，但生活史性状不同； 6) 完善的遗传资源工具箱，包括部分测序的基因组和转录组，以及有效的 RNAi 协议。在拟议的工作中，我们确定了饮食限制、氧化应激和高温对褶皱臂尾轮虫物种复合体的五种密切相关菌株的衰老和长寿的影响。有性生殖和无性生殖对衰老的影响也得到了研究，并与蛋白质、脂质和 DNA 的累积氧化损伤相关。我们还通过检查不同年龄轮虫在不同饮食、生殖和应激条件下的转录谱来鉴定与衰老和长寿有关的基因，并通过 RNAi 和 qtPCR 确认特定基因的活性。滞育在衰老中的作用也通过检查臂尾轮虫滞育改变组织稳态、在休眠期间暂停新陈代谢以及刺激休眠后组织修复的机制来研究。还检查了休眠状态长达 25 年的轮虫的衰老程度。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Glycerol extends lifespan of Brachionus manjavacas (Rotifera) and protects against stressors.

DOI：
10.1016/j.exger.2014.05.005
发表时间：
2014-09
期刊：
EXPERIMENTAL GERONTOLOGY
影响因子：
3.9
作者：
Snell, Terry W.;Johnston, Rachel K.
通讯作者：
Johnston, Rachel K.

Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations.

DOI：
10.1007/s10522-012-9371-x
发表时间：
2012-06
期刊：
BIOGERONTOLOGY
影响因子：
4.5
作者：
Snell, Terry W.;Fields, Allison M.;Johnston, Rachel K.
通讯作者：
Johnston, Rachel K.

Genetic determinants of mate recognition in Brachionus manjavacas (Rotifera).

Manjavacas（轮虫类）配偶识别的遗传决定因素。

DOI：
10.1186/1741-7007-7-60
发表时间：
2009
期刊：
BMC biology
影响因子：
5.4
作者：
Snell,TerryW;Shearer,TonyaL;Smith,HilaryA;Kubanek,Julia;Gribble,KristinE;Welch,DavidBMark
通讯作者：
Welch,DavidBMark

Genome-wide transcriptomics of aging in the rotifer Brachionus manjavacas, an emerging model system.