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

Abstract

SummaryAmong 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 senescenceassociated β β β β -galactosidase activity and a reduction in melatonin secretion. Our current data thus suggest that during the lifespan of zebrafish, the onset of senescenceassociated 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.

Autolysosome biogenesis and developmental senescence are regulated by both Spns1 and v-ATPase

“…4 Furthermore, we have established the senescence-associated Glb1/b-galactosidase (SA-Glb1) assay, which is commonly used to monitor senescence in mammalian cells, in zebrafish embryos and larvae as well as adults. 4,7,[15][16][17] The appearance of yolk opaqueness accompanied by increased SA-Glb1 activity in spns1-mutant fish embryos or larvae supports the notion that the interruption of the intrinsic nutrient supply, supposedly from autophagydependent catabolism of the yolk in zebrafish embryos and larvae, 18 may lead to profound energetic exhaustion under the aberrant autolysosomal condition resulting from Spns1 deficiency. As reported previously, we found that a specific inhibitor of the v-ATPase, bafilomycin A 1 (BafA), and several other U.S. Food and Drug Administration-approved proton-pump inhibitors such as omeprazole, lansoprazole and pantoprazole could significantly suppress the phenotypes induced by Spns1 deficiency ( Fig.…”

Tissue regeneration after injury in adult zebrafish: The regenerative potential of the caudal fin

“…While amphibians have long been the central characters employed in studies on tissue or organ regeneration (Brockes, 1997;Beck et al, 2009;Contreras et al, 2009;Kragl et al, 2009;Calve et al, 2010), the zebrafish (Danio rerio) have recently emerged as a new vertebrate model for genetic studies of tissue/ organ regeneration. Like amphibians, zebrafish exhibit an enhanced capability of regenerating adult tissues, which include retina, spinal cord, kidney, heart, and fin (Poss et al, 2000a(Poss et al, ,b, 2002aNechiporuk and Keating, 2002;Nechiporuk et al, 2003;Jazwinska et al, 2007;Schoenebeck et al, 2007;Tsai et al, 2007;Qin et al, 2009;Jopling et al, 2010;Thummel et al, 2010). Fin regeneration is a particularly efficient model for studying tissue regeneration.…”

“…In response to injury, major fin structures may regenerate very rapidly in zebrafish. For example, within a few hours post fin amputation, epidermal cells migrate and accumulate, mesenchymal cells reorganize and proliferate, and new segments progressively add to the distal end of the regenerating fin until the original length of the fin is achieved (Geraudie and Singer, 1992;Johnson and Weston, 1995;Kawakami et al, 2004;Jazwinska et al, 2007;Borday et al, 2001;Murciano et al, 2007;Tsai et al, 2007).…”

Aging of the circadian system in zebrafish and the effects of melatonin on sleep and cognitive performance

“…Recently, it has also attracted attention as a model for studying aging [ 8,13,14,27,31 ]. Under laboratory conditions, zebrafish mature within the first 6 months and survive for up to 6 years.…”

“…Under laboratory conditions, zebrafish mature within the first 6 months and survive for up to 6 years. They show age-dependent changes in multiple physiological and cognitive parameters by 2 years of age [ 27,31 ]. The presence of both central circadian oscillators (the pineal gland and eyes) and peripheral oscillators in multiple tissues [for review, 4, 6, 25 ] makes zebrafish a potentially outstanding source of information on the intrinsic and environmental factors involved in coordinating these circadian elements and their impact on aging.…”