Zebrafish as a Genetic Model in Biological and Behavioral Gerontology: Where Development Meets Aging in Vertebrates – A Mini-Review

Abstract

Understanding the molecular mechanisms of aging in vertebrates is a major challenge of modern biology and biomedical science. This is due, in part, to the complexity of the aging process and its multifactorial nature, the paucity of animal models that lend themselves to unbiased high-throughput screening for aging phenotypes, and the difficulty of predicting such phenotypes at an early age. We suggest that the zebrafish genetic model offers a unique opportunity to fill in this gap and contributes to advances in biological and behavioral gerontology. Our recent studies demonstrated that this diurnal vertebrate with gradual senescence is an excellent model in which to study age-dependent changes in musculoskeletal and eye morphology, endocrine factors, gene expression, circadian clock, sleep and cognitive functions. Importantly, we have also found that the presence of a senescence-associated biomarker (‘senescence-associated β-galactosidase’) can be documented during early zebrafish development and is predictive of premature aging phenotypes later in adult life. The availability of mutant ‘genotypes’ with identified aging ‘phenotypes’ in zebrafish, in combination with a wealth of information about zebrafish development and genetics, and the existence of multiple mutant and transgenic lines, should significantly facilitate the use of this outstanding vertebrate model in deciphering the mechanisms of aging, and in developing preventive and therapeutic strategies to prolong the productive life span (‘health span’) in humans.

Genetic Evidence of an Evolutionarily Conserved Role for Nrf2 in the Protection against Oxidative Stress

“…Cnc and Skn-1 have been reported to play a critical role in the regulation of life span in flies and worms, respectively (2,43), but the roles of Nrf2 in vertebrate longevity have not been sufficiently investigated (36). Recent studies have shown that the zebrafish is a potentially valuable model for aging research (12,24). The relationship between longevity and Nrf2 functions can be analyzed using the nrf2 fh318 mutants examined in this study.…”

Dopaminergic control of anxiety in young and aged zebrafish

“…The recent and remarkable discovery that birds and reptiles lack the DAT transporter (Lovell et al, 2015) reduces the choice of vertebrate models to mammals and fish. Among those, the diurnal vertebrate zebrafish model offers multiple advantages, including its well-developed DA system (Panula et al, 2010), gradual aging (Kishi et al, 2009) and sensitivity to multiple drugs of abuse and their withdrawal (Bencan et al, 2009; López Patiño et al, 2008a; Riley et al, 2015; Rinkwitz et al, 2011). …”

Developing ‘integrative’ zebrafish models of behavioral and metabolic disorders

“…Likewise, transgenic mouse studies show that neurodegeneration itself may contribute to obesity [253]. Given the utility of zebrafish models to study aging [254,255], obesity (Tables 2 and 3) and neurodegeneration [256,257], it is possible to expect that novel aquatic models can be useful to mimic pathogenetic interplay between metabolic and neurodegenerative disorders. With the growing population affected by obesity, AD and PD worldwide [258], this direction of zebrafish biomedical research becomes especially timely and clinically relevant.…”