Differential effects of genotoxic stress on both concurrent body growth and gradual senescence in the adult zebrafish

Abstract

Among vertebrates, fish and mammals show intriguing differences in their growth control properties with age. The potential for unlimited or indeterminate growth in a variety of fish species has prompted many questions regarding the senescent phenomena that appear during the aging process in these animals. Using zebrafish as our model system, we have attempted in our current study to examine the growth phenomena in fish in relation to the onset of senescence-associated symptoms, and to evaluate the effects of genotoxic stress on these processes. We observed in the course of these analyses that the zebrafish undergoes continuous growth, irrespective of age, past the point of sexual maturation with gradually decreasing growth rates at later stages. Animal population density, current body size and chronological age also play predominant roles in regulating zebrafish growth and all inversely influence the growth rate. Interestingly, the induction of genotoxic stress by exposure to ionizing radiation (IR) did not adversely affect this body growth ability in zebrafish. However, IR was found to chronically debilitate the regeneration of amputated caudal fins and thereby induce high levels of abnormal fin regeneration in the adult zebrafish. In addition, by resembling and mimicking the natural course of aging, IR treatments likewise enhanced several other symptoms of senescence, such as a decline in reproductive abilities, increased senescence-associated beta-galactosidase activity and a reduction in melatonin secretion. Our current data thus suggest that during the lifespan of zebrafish, the onset of senescence-associated symptoms occurs in parallel with continuous growth throughout mid-adulthood. Moreover, our present findings indicate that genotoxic DNA damage may play a role as a rate-limiting factor during the induction of senescence, but not in the inhibition of continuous, density-dependent growth in adult zebrafish.