Class I histone deacetylase HDA-3 is required for full maintenance of locomotor ability in Caenorhabditis elegans

Abstract

Locomotor ability declines with old age. A persons capacity to maintain locomotor ability depends on genetic and environmental factors. Currently, the specific genetic factors that work to maintain locomotor ability are not well understood. Here we report the involvement of hda-3, encoding a class I histone deacetylase, as a specific genetic factor that contributes to the maintenance of locomotor ability in C. elegans. From a forward genetic approach, we identified a missense mutation in HDA-3 as the causative mutation for progressive decline in locomotor ability in one of the isolated strains. From transcriptome analysis, we found downregulated expression of two clusters of genes on Chromosome II and IV in this strain. Genes carrying CUB-like domains and genes carrying BATH domains were found on Chromosome II and IV, respectively. Knockdown of CUB-like genes, K08D8.5 and dod-17, and BATH genes, bath-1, bath-21 and bath-24 led to a progressive decline in locomotor ability. Our study identifies specific genetic factors that work to maintain locomotor ability and reveals potential targets for delaying age-related locomotor decline.