Ph.D Thesis

Ph.D StudentVoskoboynik Ayelet
SubjectDevelopmental Processes and Programmed Cell Death in the
Colonial Tunicate Botryllus Schlosseri
DepartmentDepartment of Medicine
Supervisors ASSOCIATE PROF. Abraham Reznick
PROF. Baruch Rinkevich
PROF. Anna Weiss


Oxidative stress, apoptosis and aging processes are closely connected. For example: exposure of different cells to reactive oxygen species (ROS) induces apoptosis. By using antioxidant agents, these cells can be protected from apoptosis. The free radical theory of aging which connects aging and accumulation of ROS damage, is widely accepted. Administration of antioxidants, may increase the average life expectancy of some animals.

Botryllus schlosseri is a colonial sea squirt. Each colony is composed of genetically identical modules, the zooids.  As a part of its life cycle, once a week (at 18-200C), the whole functional zooids are resorbed and replaced by their buds and the zooid resorbtion is taking place mainly by apoptotic processes. B. schlosseri colonies also exhibit non-random life span, and ramets (clonal replicates), experimentally separated from parent colonies, die almost simultaneously with their parent colonies.

A single short but acute treatment with high doses of the antioxidant Butylated Hydroxy Toluene (BHT), caused zooids to be arrested in the apoptotic final phase, the stage of dead cells removal by phagocytes. Intrestingly, significant high numbers of empty macrophage cells were observed in the treated ramets. Concomitantly, addition of BHT reduced the general oxidative levels of proteins and lipids. It seems that the antioxidant BHT has inhibitory effect on the phagocyte. In addition the BHT treated ramets presented an unprecedented growth rates and life span lengthening. For example, an average of 49.2% life span extension was recorded in the treated ramets. It seems that oxidative reactions are involved in the final removal of zooids by phagocytes and also alterations in the oxidative status of these animals by BHT treatment, can set up a new genetic clock of life extension.