Titlecelsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish.
Publication TypeJournal Article
Year of Publication2020
AuthorsLi, C, Barton, C, Henke, K, Daane, J, Treaster, S, Caetano-Lopes, J, Tanguay, RL, Harris, MP
JournalElife
Volume9
Date Published2020 Jan 27
ISSN2050-084X
KeywordsAging, Aging, Premature, Animals, Animals, Genetically Modified, Cadherins, Female, Homeostasis, Male, Mutation, Phenotype, Stem Cells, Zebrafish, Zebrafish Proteins
Abstract

The use of genetics has been invaluable in defining the complex mechanisms of aging and longevity. Zebrafish, while a prominent model for vertebrate development, have not been used systematically to address questions of how and why we age. In a mutagenesis screen focusing on late developmental phenotypes, we identified a new mutant that displays aging phenotypes at young adult stages. We find that the phenotypes are due to loss-of-function in the non-classical cadherin . The premature aging is not associated with increased cellular senescence or telomere length but is a result of a failure to maintain progenitor cell populations. We show that is essential for maintenance of stem cell progenitors in late stages. Caloric restriction can ameliorate aging phenotypes. These data suggest that function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.

DOI10.7554/eLife.50523
Alternate JournalElife
PubMed ID31985398
PubMed Central IDPMC7010407
Grant List2R01DE019837-09 / NH / NIH HHS / United States