Genetic loci and metabolic states associated with murine epigenetic aging.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research in mice
PubMed 35389339 · doi:10.7554/eLife.75244
What was done
Researchers profiled highly conserved CpGs using a pan-mammalian microarray in 339 predominantly female mice from the BXD genetic reference panel with existing longevity and genomic data. They computed epigenetic clocks and evaluated associations between DNA methylation (DNAm) entropy, high-fat diet, body weight, metabolic parameters, and genetic variation, alongside transcriptomic and proteomic analyses.
What was found
High-fat diet augmented age-related DNAm changes. DNAm entropy increased with age, and progression toward epigenetic disorder (particularly at CpGs gaining methylation over time) predicted genotype-dependent life expectancy, with longer-lived BXD strains exhibiting lower entropy at a given age. The authors identified two quantitative trait loci modulating epigenetic age acceleration (EAA): one on Chromosome 11 containing the Erbb2/Her2 oncogenic region, and one on Chromosome 19 containing a cytochrome P450 cluster. These loci contain genes associated with human EAA (including STXBP4, NKX2-3, and CUTC). Transcriptomic and proteomic analyses correlated EAA with oxidation-reduction, metabolic, and immune response pathways. No specific effect sizes, p-values, or correlation coefficients were provided in the abstract.
Why it matters
This study identifies specific, evolutionarily conserved genetic loci and metabolic factors that regulate epigenetic aging rates, demonstrating shared biological mechanisms controlling epigenetic aging between rodents and humans.
Limits
The study was conducted in mice and was restricted predominantly to female animals. The abstract provides no exact numerical values, effect sizes, or confidence intervals, and findings require further functional validation in human populations.
Cited by
- supports Caloric restriction slows epigenetic aging in mice, while a high-fat diet accelerates epigenetic aging in mice.