Cell-type-specific effects of age and sex on human cortical neurons.
Neuron
; 112(15): 2524-2539.e5, 2024 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-38838671
ABSTRACT
Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
/
Neurônios
Limite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Neuron
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos