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

Yifei Weng1,2, Coleen T Murphy1,2

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Keywords:
Biological sciencesCellular neuroscienceDevelopmental neuroscienceMolecular neuroscienceNatural sciencesNeuroscience

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Area of Science:

  • Neuroscience
  • Genetics
  • Aging Research

Background:

  • Cognitive aging is a complex biological process with known sex-based differences.
  • While cognitive aging in Caenorhabditis elegans hermaphrodites is studied, male cognitive decline remains less understood.

Purpose of the Study:

  • To investigate sex-shared and sex-dimorphic characteristics of cognitive aging in C. elegans.
  • To identify neuron-specific, age-associated, sex-differential gene targets.
  • To elucidate the molecular mechanisms underlying sexual dimorphism in cognitive aging.

Main Methods:

  • Comparative analysis of gene expression in aging male and hermaphrodite C. elegans.
  • Identification of differentially expressed genes and pathways.
  • Functional analysis of candidate genes, such as hrg-7, in behavioral assays.

Main Results:

  • Cognitive aging exhibits both shared and sex-specific features.
  • Males show age-related downregulation of mitochondrial genes and upregulation of GPCR genes.
  • Hermaphrodites display increased X chromosome expression and altered dosage compensation complex expression with age.
  • The gene hrg-7 specifically regulates male cognitive aging.

Conclusions:

  • Male and hermaphrodite C. elegans exhibit distinct age-related neuronal alterations.
  • X chromosome dysregulation may contribute to sexual dimorphism in cognitive aging.
  • Identifying sex-specific pathways can inform therapeutic strategies for age-related cognitive decline in both sexes.