An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning
- Stanford University, United States
- Thielvoldt Engineering, United States
Abstract
The African turquoise killifish is an exciting new vertebrate model for aging studies. A significant challenge for any model organism is the control over its diet in space and time. To address this challenge, we created an automated and networked fish feeding system. Our automated feeder is designed to be open-source, easily transferable, and built from widely available components. Compared to manual feeding, our automated system is highly precise and flexible. As a proof-of-concept for the feeding flexibility of these automated feeders, we define a favorable regimen for growth and fertility for the African killifish and a dietary restriction regimen where both feeding time and quantity are reduced. We show that this dietary restriction regimen extends lifespan in males (but not in females) and impacts the transcriptomes of killifish livers in a sex-specific manner. Moreover, combining our automated feeding system with a video camera, we establish a quantitative associative learning assay to provide an integrative measure of cognitive performance for the killifish. The ability to precisely control food delivery in the killifish opens new areas to assess lifespan and cognitive behavior dynamics and to screen for dietary interventions and drugs in a scalable manner previously impossible with traditional vertebrate model organisms.
Data availability
This study's data are included in the submitted manuscript and supporting files. Source data have been provided as a compressed directory of supporting tables that correspond to figures as indicated in figure legends. All the scripts for analyzing the RNA-seq datasets and the behavioral assay can be accessed on GitHub. RNA-seq data have been deposited in GEO (accession number: GSE216369)..
-
An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learningGene Expression Omnibus (GEO), accession number: GSE216369.
Article and author information
Author details
Funding
Stanford Brain Rejuvenation Program
- Tony Wyss-Coray
- Anne Brunet
Stanford Graduate Fellowship
- Andrew McKay
Helen Hay Whitney Fellowship
- Claire Nicole Bedbrook
National Institutes of Health (RF1AG057334)
- Anne Brunet
National Institutes of Health (R01AG063418)
- Anne Brunet
Jane Coffin Childs Memorial Fund for Medical Research (61-1762)
- Jingxun Chen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animals were housed within the Stanford Research Animal Facility and treated in accordance with protocols approved by the Stanford Administrative Panel on Laboratory Animal Care (protocol # APLAC- 13645).
Copyright
© 2022, McKay et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,307
- views
-
- 266
- downloads
-
- 15
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning
eLife 11:e69008.
https://doi.org/10.7554/eLife.69008
Further reading
-
- Cancer Biology
- Genetics and Genomics
The expression of eukaryotic genes relies on the precise 3'-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers – particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation – have received less attention. Here, we systematically analysed somatic mutations affecting 3'UTR polyadenylation signals in human cancers using the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. We found a striking enrichment of cancer-specific somatic mutations that disrupt strong and evolutionarily conserved cleavage and polyadenylation signals within tumour suppressor genes. Further bioinformatics and experimental analyses conducted as a part of our study suggest that these mutations have a profound capacity to downregulate the expression of tumour suppressor genes. Thus, this work uncovers a novel class of noncoding somatic mutations with significant potential to drive cancer progression.
-
- Developmental Biology
- Genetics and Genomics
O-GlcNAcylation is an essential intracellular protein modification mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations in OGT have been linked to intellectual disability, indicating that this modification is important for the development and functioning of the nervous system. However, the processes that are most sensitive to perturbations in O-GlcNAcylation remain to be identified. Here, we uncover quantifiable phenotypes in the fruit fly Drosophila melanogaster carrying a patient-derived OGT mutation in the catalytic domain. Hypo-O-GlcNAcylation leads to defects in synaptogenesis and reduced sleep stability. Both these phenotypes can be partially rescued by genetically or chemically targeting OGA, suggesting that a balance of OGT/OGA activity is required for normal neuronal development and function.
