Comprehensive Aging Atlas of Mammary Tissues Links Aging to Cancer Risk

SciFocus/Nov 28, 2024 -- Aging is the most significant risk factor for breast cancer, yet the precise mechanisms linking the aging process to cancer development have remained elusive. A groundbreaking study published in Nature Aging provides a detailed single-cell atlas of how mammary tissues age, offering insights into the shared molecular and cellular signatures of aging and cancer.

"By mapping cellular and molecular changes in aging mammary tissues, we’ve uncovered key insights into how the aged microenvironment may contribute to cancer risk. This resource bridges the gap between aging biology and cancer research."

Key Highlights

Aging-Induced Molecular Changes:

• Epigenetic and transcriptional changes in epithelial cells, with shifts in genes related to metabolism, inflammation, and cancer.
• Stromal cells show markers of senescence and cancer-associated fibroblast activation.

Immune Cell Alterations:

• Expansion of specific immune subsets, including Gzmk+ T cells, memory CD4+ T cells, γδ T cells, and M2-like macrophages.
• Spatial transcriptomics revealed co-localization of aged immune and epithelial cells, suggesting an altered tissue microenvironment.

Cross-Species Relevance: Aging-related signatures identified in mouse mammary cells were found in human breast tumors, highlighting potential translational links between aging and cancer risk.

Cellular Plasticity and Lineage Fidelity: Aging disrupted cellular identity markers in epithelial, stromal, and immune cells, suggesting increased cell plasticity that may predispose tissues to neoplastic transformation.

Future Directions:

• The atlas lays the groundwork for studying how hormonal changes (e.g., menopause) and parity influence mammary aging.
• Insights from this study can inform strategies for early cancer prevention and therapeutic interventions targeting the aged microenvironment.

This study not only enhances our understanding of mammary gland aging but also serves as a vital resource for identifying potential therapeutic targets to mitigate age-related cancer risks.

Source: https://www.nature.com/articles/s43587-024-00751-8#Sec11

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