Gene expression changes in aging Zebrafish (Danio rerio) brains are sexually dimorphic

Abstract

BackgroundBrain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish has recently become a popular model organism for examining aging and age-related diseases because as in humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the aging brain that may contribute to these declines and none have examined them within individuals with respect to gender. Our aim was to identify the main genetic pathways associated with zebrafish brain aging across gender. We chose males and females from specific age groups (young, 7.5-8.5 months and old, 31-36 months) based on the progression of cognitive decline in zebrafish. RNA was isolated from individual brains and subjected to microarray and qPCR analysis. Statistical analyses were performed using a two-way ANOVA and the relevant post-hoc tests.ResultsOur results demonstrated that in the brains of young and old male and female zebrafish there were over 500 differentially expressed genes associated with multiple pathways but most notably were those related to neurogenesis and cell differentiation, as well as brain and nervous system development.ConclusionsThe gene expression of multiple pathways is altered with age and differentially expressed in males and females. Future studies will be aimed at determining the causal relationships of age-related changes in gene expression in individual male and female brains, as well as possible interventions that counteract these alterations.

Evidence of an Association between Age-Related Functional Modifications and Pathophysiological Changes in Zebrafish Heart

“…A limitation of the current research is that the zebrafish life span data in the present study did not include sex-specific data although sex-specific differences in behavior [40] and gene expression [8] have been reported in aging. Also, although female zebrafish were used in the initial population, accurate sex determination based upon subjective morphological criteria such as the criteria we used is difficult to ascertain with certainty in zebrafish.…”

“…Its short life span, transparent embryo, gradual physiological aging, and amenability to genetic engineering have caused it to be used for many development and disease studies. Like humans, aged zebrafish have reduced exercise tolerance [5], degenerative changes in the spinal column [6], and cognitive decline [7,8]. And like humans, differences in genetics have been shown to contribute to differences in life span [9].…”

Mitochondrial maintenance failure in aging and role of sexual dimorphism

“…Consistent with this scenario is the up-regulated basal expression of the proteotoxicity response, including heat shock proteins (Hsps) targeted to the cytoplasm and mitochondria [51–56]. Gene expression changes during aging are also sexually-dimorphic, for example, in the vertebrate liver [57], brain [45, 58] and heart [59, 60], where males tend to show relatively greater reduction in mitochondrial gene expression.…”

Cell Electrical Impedance as a Novel Approach for Studies on Senescence Not Based on Biomarkers

“…However, further studies may be required to enhance the accuracy of measurement by this methodology. Future experiments should be carried out on the senescent change of mammal cells and also include in vivo tests to determine ways to minimize the effect of devascularized cells on the changes in their electrical properties [23], and sex-specific tests should be carried out to improve the discrimination capability of cell impedance [32]. …”