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Updated: Jun 27, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Single-cell epigenomics uncovers heterochromatin instability and transcription factor dysfunction during mouse brain
Maria Luisa Amaral1, Sainath Mamde2, Michael Miller3
1Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Brain aging involves widespread transcriptional changes and loss of heterochromatin maintenance, affecting cellular identity and highlighting vulnerable pathways. This study reveals key molecular mechanisms driving brain aging across different cell types and regions.
Area of Science:
- Neuroscience
- Genomics
- Epigenetics
Background:
- Mechanisms of transcriptional regulation during brain aging are not well understood.
- Aging impacts cellular identity and function in the brain.
Purpose of the Study:
- To investigate age-associated changes in chromatin accessibility and gene expression across mouse brain regions.
- To identify cell-type and region-specific molecular alterations during brain aging.
Main Methods:
- Single-cell epigenomics was employed to profile chromatin accessibility and gene expression.
- Analysis was conducted across eight mouse brain regions at three different ages (2, 9, and 18 months).
Main Results:
- Observed decline in progenitor populations for neurogenesis and myelination.
- Widespread age-associated changes in transcription and chromatin accessibility in neuronal and glial cells.
- Dysregulation of master transcription factors and shift towards activator protein 1 (AP-1) driven stress-response programs.
- Identified region- and cell-type-specific heterochromatin loss, transposable element activation, and long noncoding RNA upregulation, especially in glutamatergic neurons.
Conclusions:
- Brain aging disrupts heterochromatin maintenance and transcriptional regulation.
- Progressive drift in cellular identity occurs with aging.
- Specific brain regions, cell types, and molecular pathways are vulnerable during aging.
