The zebrafish as a vertebrate model of functional aging and very gradual senescence

Abstract

The zebrafish ( Danio rerio) has been developed as a powerful model for genetic studies in developmental biology, which also gives insights into several diseases of adult humans such as cardiovascular disease and cancer. Because aging processes affect these and many other human diseases, it is important to compare zebrafish and other mammalian aging. However, the aging process of zebrafish remains largely unexplored, and little is known about its functional aging and senescence. In a survey of aging in zebrafish, we detected senescence-associated β-galactosidase activity in skin and oxidized protein accumulation in muscle. However, we did not observe lipofuscin granules (‘aging pigments’), which commonly accumulate in postmitotic cells of other vertebrates. This absence of lipofuscins may be consistent with the existence of continuously proliferating myocytes that incorporated BrdU in muscle tissues of aged zebrafish. Moreover, we demonstrated that zebrafish have constitutively abundant telomerase activity in somatic tissues from embryos to aged adults. Although some stress-associated markers are upregulated and minor histological changes are observed during the aging process of zebrafish, our studies together with other evidence of remarkable reproductive and regenerative abilities suggest that zebrafish show very gradual or sub-negligible senescence in vivo.