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Cell-type-specific effects of age and sex on human cortical neurons.
- Source :
-
Neuron [Neuron] 2024 Aug 07; Vol. 112 (15), pp. 2524-2539.e5. Date of Electronic Publication: 2024 Jun 04. - Publication Year :
- 2024
-
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.<br />Competing Interests: Declaration of interests J.R.E. serves on the scientific advisory board of Zymo Research Inc.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Female
Male
Adult
Aged
Young Adult
Aging physiology
Aging genetics
Sex Characteristics
Middle Aged
Epigenesis, Genetic
Transcriptome
Age Factors
Aged, 80 and over
Frontal Lobe metabolism
Frontal Lobe cytology
X Chromosome Inactivation genetics
Cerebral Cortex cytology
Cerebral Cortex metabolism
Neurons metabolism
Neurons physiology
DNA Methylation
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 112
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 38838671
- Full Text :
- https://doi.org/10.1016/j.neuron.2024.05.013