Related Experiment Video
Updated: Jun 8, 2025
12:25
Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
Published on: February 24, 2023
794
Multiomic profiling reveals timing of menopause predicts prefrontal cortex aging and cognitive function.
Fatima Gunter-Rahman1,2, Charleen D Adams3, Ravikiran M Raju4,5
1Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Aging Cell
|November 6, 2024
Summary
Later age at menopause (AAM) is linked to better brain aging and cognitive function. This ovarian aging marker may predict dementia risk, with gut microbiome changes playing a role.
Area of Science:
- Neuroscience
- Genetics
- Metabolomics
Background:
- Dementia diagnosis is frequent, and predicting risk beyond age is difficult.
- Aging processes across organ systems may offer insights for early dementia detection.
- Identifying early biomarkers is crucial for timely intervention against cognitive decline.
Purpose of the Study:
- To investigate if the timing of menopause, a marker of ovarian aging, predicts brain aging and cognitive function later in life.
- To explore the molecular mechanisms, including genetic and metabolic pathways, linking age at menopause (AAM) to brain health.
Main Methods:
- Analysis of "omics" data (genomics, transcriptomics, metabolomics) from post-mortem brain samples of 2086 subjects.
- Calculation of pre-frontal cortex aging acceleration using DNA methylation.
- Examination of gene expression and metabolite profiles in relation to age at menopause (AAM) and menopausal type (natural vs. surgical).
Main Results:
- Later age at menopause (AAM) positively correlated with cognitive function and negatively with brain aging acceleration.
- Shared heritability partially explains the association between AAM and cognitive function.
- Later AAM was linked to gene expression in the pre-frontal cortex associated with better cognition and reduced aging pathways (natural menopause).
- Surgical menopause showed distinct molecular changes, including altered nicotinamide adenine dinucleotide (NAD+) activity and perturbed bile acid metabolism.
- Bile acid metabolism was altered in both menopausal groups, with different ratios associated with AAM.
Conclusions:
- Age at menopause (AAM) serves as a predictive marker for brain aging and cognitive function.
- The gut microbiome may mediate the link between AAM and cognitive decline, with distinct mechanisms for natural versus surgical menopause.
- These findings highlight potential early biomarkers for dementia risk assessment.
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