Systematic dissection of epigenetic age acceleration in normal breast tissue reveals its link to estrogen signaling and cancer risk
Sehl, M. E.; Guo, W.; Farrell, C.; Marino, N.; Henry, J. E.; Storniolo, A. M.; Papp, J.; Li, J. J.; Horvath, S.; Pellegrini, M.; Ganz, P. A.
Show abstract
Breast aging encompasses intricate molecular and cellular changes that elevate cancer risk. Our study profiled DNA methylation and gene expression of 181 normal breast samples and systematically evaluated eight epigenetic clocks. We found that clocks trained using breast tissues demonstrate improved age prediction in normal breast tissue, and bias universally exists in epigenetic clocks, necessitating a proper definition of age acceleration. Cell composition analysis revealed significant age-related alterations and highlighted its distinct associations with age acceleration, including increased luminal epithelial and myoepithelial cells and reduced adipocytes and immune cells, connecting age acceleration to carcinogenesis from a cell compositional perspective. Additionally, CpG sites associated with age acceleration were enriched for estrogen receptor binding sites, providing a mechanistic link between estrogen exposure, accelerated aging, and cancer. These findings highlight the importance of cellular heterogeneity in epigenetic age estimates and the potential of age acceleration to guide for risk stratification and prevention strategies.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors 96%
- Nature of epigenetic aging from a single-cell perspective 96%
- Multimodal data analysis reveals asynchronous aging dynamics across female reproductive organs 95%
Similar papers in this journal
- voyAGEr: free web interface for the analysis of age-related gene expression alterations in human tissues 96%
- Rat leukocyte population dynamics predicts a window for intervention in aging. 96%
- Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.