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.

Public Health Relevance

These studies are designed to dissect the aging process in a new model organism, the colonial ascidian Botryllus schlosseri. Botryllus is a Chordate, and belongs to a group of species that are the precursors of the vertebrates. The larval form of ascidians is a chordate tadpole, but that soon metamorphoses into an invertebrate adult, which has a complex body plan that includes a heart, pharynx, GI tract, nervous system, complex vasculature and blood. Botryllus belongs to a subset of ascidians that are colonial, and grow, not by increasing in size, but by regenerating entire bodies, including all tissues, each and every week. This results in a colony of genetically identical individuals linked by a common blood supply. One of the most powerful aspects of Botryllus as a model for aging is that each individual can be separated into several pieces and will continue to grow. Thus we can study pieces of an individual independently, comparing regenerative abilities over time, as the colony ages. In addition, Botryllus also has several other interesting aging characteristics, including two distinct lifespans in both lab-reared and natural populations (3 mos. and 1 yr), as well as both random and non-random senescence of separated pieces of a single individual. Over the last 15 years we have been developing contemporary genetic and genomic tools to dissect these processes, allowing us to utilize the unique life history traits and short lifespan and of this chordate model. Studying the aging process in this simpler, ancestral organism will provide opportunities and insights not available in other species.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG037966-04
Application #
8529423
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (M1))
Program Officer
Murthy, Mahadev
Project Start
2010-09-01
Project End
2015-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$331,327
Indirect Cost
$107,933
Name
University of California Santa Barbara
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106
Langenbacher, Adam D; Rodriguez, Delany; Di Maio, Alessandro et al. (2015) Whole-mount fluorescent in situ hybridization staining of the colonial tunicate Botryllus schlosseri. Genesis 53:194-201
Taketa, Daryl A; De Tomaso, Anthony W (2015) Botryllus schlosseri allorecognition: tackling the enigma. Dev Comp Immunol 48:254-65
Braden, Brian P; Taketa, Daryl A; Pierce, James D et al. (2014) Vascular regeneration in a basal chordate is due to the presence of immobile, bi-functional cells. PLoS One 9:e95460
Nydam, Marie L; Netuschil, Nikolai; Sanders, Erin et al. (2013) The candidate histocompatibility locus of a Basal chordate encodes two highly polymorphic proteins. PLoS One 8:e65980
Carpenter, Meredith A; Powell, John H; Ishizuka, Katherine J et al. (2011) Growth and long-term somatic and germline chimerism following fusion of juvenile Botryllus schlosseri. Biol Bull 220:57-70