Male-specific behavioral and transcriptomic changes in aging C. elegans neurons

Yifei Weng, Coleen T. Murphy

Research output: Contribution to journalArticlepeer-review

Abstract

Aging is a complex biological process with sexually dimorphic aspects. Although cognitive aging of Caenorhabditis elegans hermaphrodites has been studied, less is known about cognitive decline in males. We found that cognitive aging has both sex-shared and sex-dimorphic characteristics, and we identified neuron-specific age-associated sex-differential targets. In addition to sex-shared neuronal aging genes, males differentially downregulate mitochondrial metabolic genes and upregulate GPCR genes with age, while the X chromosome exhibits increased gene expression in hermaphrodites and altered dosage compensation complex expression with age, indicating possible X chromosome dysregulation that contributes to sexual dimorphism in cognitive aging. Finally, the sex-differentially expressed gene hrg-7, an aspartic-type endopeptidase, regulates male cognitive aging but does not affect hermaphrodites’ behaviors. These results suggest that males and hermaphrodites exhibit different age-related neuronal changes. This study will strengthen our understanding of sex-specific vulnerability and resilience and identify pathways to target with treatments that could benefit both sexes.

Original languageEnglish (US)
Article number109910
JournaliScience
Volume27
Issue number6
DOIs
StatePublished - Jun 21 2024

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Biological sciences
  • Cellular neuroscience
  • Developmental neuroscience
  • Molecular neuroscience
  • Natural sciences
  • Neuroscience

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