Age-Associated Different Transcriptome Profiling in Zebrafish and Rats: an Insight into the Diversity of Vertebrate Aging

Abstract

Background: Aging and death are inevitable for most species and are of intense interest for human beings. Most mammals, including humans, show obvious aging phenotypes, for example, loss of tissue plasticity and sarcopenia. In this regard, fish provide attractive models because of their unique aging characteristics. First, the lifespan of fish is highly varied and some long-lived fish can live for over 200 years. Second, some fish show anti-aging features and indeterminate growth throughout their life.Because these characteristics are not found in mammalian model organisms, exploring mechanisms of senescence in fish is expected to provide new insights into vertebrate aging. Therefore, we conducted transcriptome analysis for brain, gill, heart, liver and muscle from 2-month-, 7-month-, 16month-and 39-month-old zebrafish. In addition, we downloaded RNA-seq data for sequential agerelated gene expression in brain, heart, liver and muscle of rat (1). These RNA-seq data from two species were compared, and common and species-specific features of senescence were analyzed.Results: Screening of differentially expressed genes (DEGs) in all zebrafish tissues examined revealed up-regulation of circadian genes and down-regulation of hmgb3a. Comparative analysis of DEG profiles associated with aging between zebrafish and rat showed both conserved and clearly different aging phenomena. Furthermore, up-regulation of circadian genes with aging and down-regulation of collagen genes were observed in both species. On the other hand, in zebrafish, up-regulation of autophagy related genes in muscle and atf3 in various tissues suggested fish-specific anti-aging characteristics. Consistent with our knowledge of mammalian aging, a tissue deterioration-related DEG profile was observed in rat. We also detected aging-associated down-regulation of muscle development and ATP metabolism-related genes in zebrafish gill. Correspondingly, hypoxia-related genes were systemically up-regulated in aged zebrafish, suggesting age-related hypoxia as a senescence modulator in fish. Conclusions:Our results indicate both common and different aging profiles between fish and mammals. Gene expression profiles specific to fish will provide new insight for future translational research.

Inflammation in Development and Aging: Insights from the Zebrafish Model

“…Together with unquestionable advantages compared to other vertebrate models, such as rapid development, high fecundity, transparency, and ease of gene editing, the zebrafish is a powerful animal model to study a great variety of human diseases. Some of the fields in which zebrafish have proven particularly valuable are the study of the role of inflammation in host defense, immune responses, development, tissue regeneration, and aging [2][3][4][5][6][7]. Inflammation can be triggered by several sources, including biological, chemical, and mechanical, and these have been largely employed in zebrafish models to address molecular and cellular questions, particularly in pathogenic conditions.…”

“…According to the World Health Organization, more than 10% of the world's population is over 60 years old, and by 2050, it will nearly double. Zebrafish is a promising model in the field to study different age-related diseases due to its genetic and physiological similarities to humans [5,146,147].…”

Zebrafish as an Emerging Model for Sarcopenia: Considerations, Current Insights, and Future Directions

“…This diminutive aquatic organism has earned its place as an indispensable model organism for investigating crucial pathways and therapeutics associated with various facets of human health, such as neurodegenerative disorders, skeletomuscular ailments, and cardiovascular conditions [1][2][3][4]. Genetically, the zebrafish genome shares an astonishing 70% similarity with the human genome, with approximately 82% of genes associated with human ailments having identifiable orthologues in zebrafish [5,6].…”

“…Primary sarcopenia, a condition characterized by the age-related loss of muscle mass and function, which significantly compromises the quality of life in affected individuals, has been extensively studied utilizing model organisms, including mice, rats, flies, and worms. These models have facilitated the identification of therapeutic strategies and genetic modifications aimed at ameliorating muscle-related degenerative processes in aging individuals [6]. However, practical diagnostic modalities, accurate biomarkers for risk stratification or follow-up, and effective treatments for primary sarcopenia are still elusive.…”

“…Despite the apparent senescence and fixed lifetime of mammalian skeletal muscle, fish tissues maintain significant plasticity even at the adult stage. This allows researchers to examine the metabolic functions such as peroxisome-resident proteins using morpholino-mediated knockdown or transcription activator-like effector nucleases [6][7][8].…”