Single-cell spatial atlas of the aging human breast

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Breast cancer incidence and tumor characteristics vary with patient age.
• Aging significantly impacts tissue structure and cellular function, but breast tissue aging is poorly understood.
• The spatial context of early tumors is influenced by aging, potentially explaining age-related differences in breast cancer.

Purpose of the Study:

• To characterize age-related remodeling in normal human breast tissues.
• To investigate how aging affects breast tissue cellularity, proliferation, architecture, and microenvironment.
• To create a multiscale spatial atlas of aging breast tissue.

Main Methods:

• Analysis of over 3 million cells from 527 reduction mammoplasty samples.
• Utilized imaging mass cytometry to profile the spatial expression of 40 proteins.
• Examined age-related changes in epithelial, stromal, and immune cell populations and their interactions.

Main Results:

• Aged breast tissue exhibited reduced cellularity and proliferation across all cell types.
• Tissue architecture showed fewer lobules, increased fat content, and altered epithelial cell-cell interactions.
• Older tissues presented a more inflammatory microenvironment with increased M2 macrophages and Granzyme B+ T cells, while younger tissues were enriched in B cells.

Conclusions:

• Aging leads to a general decline in breast tissue health and a significant restructuring of its spatial context.
• These age-related changes in breast tissue may influence the development and characteristics of breast cancer in different age groups.
• The study provides a comprehensive spatial atlas detailing the aging process in breast tissue.