Aging and Regeneration in a basal chordate

描述（由申请人提供）：旨在确定衰老机制的理论大致可分为两类。第一种将衰老归因于分子和细胞机制的逐渐退化，最终通过破坏生理稳态而导致死亡；磨损模型。第二种观点认为，寿命是由基因决定的，因此衰老可能源于内在的过程，这些过程为生物体的生存能力提供了一个非随机的、最终的时间间隔。我们正在研究一种具有这两种特性的生物：群集海鞘，Botryllus schlosseri。bottryllus属于Tunicata门，是脊椎动物的姊妹类群。除了这种密切的系统发育关系外，Botryllus还具有许多生活史性状，使其成为研究衰老的良好模型。首先，Botryllus有一个群体生活史，通过无性繁殖的过程生长，在这个过程中，整个身体，包括所有的体细胞和种系，每周都会再生，形成一个基因相同的个体群体。一个菌落可以分裂成多个片段，并将继续生长，从而可以在单个基因型的一生中对遗传变化进行表征。此外，负责再生的干细胞可以随着时间的推移而丰富并具有遗传和功能变化的特征。其次，先前对遗传上不同的Botryllus谱系的寿命研究表明，存在与繁殖努力和其他生活史特征无关的直接遗传基础。我们最近开发了遗传和基因组工具来识别和功能表征参与这一过程的基因，包括一个大型转录组数据库，它将为衰老过程中全面的基因分析提供起点，允许识别参与再生和衰老的候选基因，然后可以在不同衰老表型的个体的寿命中进行分析。此外，我们已经建立了进行正向和反向基因筛选的基础设施。利用这些工具，我们将开始识别和表征这种新型脊索动物模式生物衰老的遗传基础。

DESCRIPTION (provided by applicant): Theories which aim to identify the mechanisms of aging can be broadly classified into two groups. The first attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis; the wear-and-tear model. The second suggests that life span is genetically programmed, and therefore aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus belongs to the phylum Tunicata, the sister group to the vertebrates. Besides this close phylogenetic relationship, Botryllus has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. A colony can be split into multiple pieces and will continue to grow, allowing the characterization of genetic changes over the lifetime of a single genotype. In addition, the stem cells responsible for regeneration can be enriched and characterized for both genetic and functional changes over time. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. We have recently developed the genetic and genomic tools to identify and functionally characterize genes involved in this process, including a large transcriptome database which will provide a starting point for comprehensive gene profiling during aging, allowing the identification of candidate genes involved in regeneration and aging, which can then be analyzed over the lifespan of individuals of different aging phenotypes. In addition, we have created the infrastructure to carry out both forward and reverse genetic screens. Using these tools we will begin to identify and characterize the genetic basis of aging in this novel chordate model organism.