AGEING rewires the cellular and molecular landscape of mammary glands, increasing the risk of breast cancer through epigenetic, transcriptional, and immune changes. This study provides critical insights into how age-related shifts in cell identity and microenvironment contribute to cancer initiation, offering a valuable resource for ageing and cancer biology.
Using single-cell RNA sequencing and spatial transcriptomics, researchers analysed the mammary glands of aged mice, uncovering significant changes in epithelial, stromal, and immune cells. Aged epithelial cells showed altered expression of metabolic, pro-inflammatory, and cancer-associated genes, while stromal cells downregulated fibroblast markers and upregulated senescence and cancer-associated fibroblast signatures. Immune cell populations also shifted, with expansions in Gzmk+ T cells, memory CD4+ T cells, γδ T cells, and M2-like macrophages. Spatial analysis revealed co-localization of aged immune and epithelial cells, suggesting a pro-tumorigenic microenvironment. Importantly, transcriptional signatures of aged mouse mammary cells were also found in human breast tumours, highlighting potential links between ageing and cancer.
These findings underscore the profound impact of ageing on mammary gland biology, with implications for clinical practice. Understanding these age-related changes could lead to better risk stratification and early detection strategies for patients with breast cancer. Future research should explore therapeutic interventions targeting the aged microenvironment to mitigate cancer risk, particularly in older patients. This study lays the groundwork for translating these insights into clinical applications, potentially improving outcomes for ageing populations.
Katheeja Imani, EMJ
Reference
Angarola BL et al. Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer. Nat Aging. 2025;5(1):122-43.
