Aging in the Primitive Chordate, Botryllus schosseri

T. De Tomaso
Hopkins Marine Station, Stanford University, Pacific Grove, CA

The key physiological characteristic of aging is a failure to maintain tissue integrity due to progressive deterioration, coupled to the apparent exhaustion of normal regenerative potential. This may be due to environmental factors, such as DNA damage, which eventually cannot be overcome, and/or genetic components may exist that enforce intrinsic processes within an individual. We are developing a new model organism to study aging in which both characteristics are present and can be experimentally manipulated: an ascidian, or sea squirt, called Botryllus schlosseri.

Ascidians are marine organisms that are modern-day representatives of the first ancestral vertebrates. They begin their life as a swimming tadpole larva which has many vertebrate characteristics, such as a notochord and a dorsal hollow nerve tube, but this form soon settles and undergoes a dramatic metamorphosis into a sessile, invertebrate adult body. In addition, Botryllus belongs to a subset of ascidians which are colonial, meaning that they grow, not by increasing in size, but by asexually regenerating new individuals, eventually giving rise to a colony of genetically identical individuals. The Botryllus life history is characterized by massive cyclical regeneration: each week, each individual reproduces itself, including all somatic and germline tissues. These asexually-derived individuals are autonomous, with their own heart, gut, nervous system, etc., and are not dependent on the rest of the colony for survival. Thus individual pieces of a colony can be surgically separated and will continue to grow, allowing us to analyze an individual repeatedly throughout its lifespan. This regenerative potential is due to the presence of long-lived somatic and germline stem cells which can be isolated and transplanted; and Botryllus is the closest related species to the vertebrates which can reproduce asexually.

Given this tremendous and ongoing regeneration, how does an individual genotype age? We will be talking about two distinct aging mechanisms: the first regards the lifespan of an individual within a colony, which appears fixed, while the second regards the lifespan of the genotype. For the latter, recent experiments have been focused on transplantation of somatic stem cells from juvenile individuals into adults. Current results will be discussed.