A groundbreaking study by The Jackson Laboratory (JAX) has created a comprehensive atlas of how healthy breast tissue ages, shedding light on key cellular, molecular, and genetic changes that may contribute to breast cancer development. The findings, published in Nature Aging, offer valuable insights into the link between aging and cancer risk.
Aging, while a privilege, also increases the risk of developing age-related diseases, including cancer. Researchers at The Jackson Laboratory (JAX) have made a significant breakthrough by creating a comprehensive atlas of how healthy breast tissue ages. This atlas reveals key cellular, molecular, and genetic changes that may contribute to breast cancer development.
Published in Nature Aging, the findings provide a valuable open-access resource for the scientific community to study aging and its role in cancer risk.Utilizing cutting-edge single-cell and spatial transcriptomics technologies, the research team, co-led by Olga Anczukow, Ph.D., compared young virgin female mice to older mice. They meticulously mapped the changes in the mammary gland cellular landscape over time. The team discovered that epithelial, immune, and stromal cells, crucial for maintaining healthy breast tissue, undergo significant shifts, not only in their numbers but also in their molecular identity. Furthermore, for the first time, Anczukow and her team established a direct link between aging-related gene expression changes and chromatin accessibility in the mammary gland. Chromatin accessibility refers to how tightly or loosely DNA is packed within the nucleus, influencing which genes can be activated or deactivated. Changes in chromatin structure, such as those observed during aging, might lead to the dysregulation of genes involved in cell proliferation, DNA repair, and immune response – mechanisms known to contribute to tumor growth. This groundbreaking research reveals that alterations in chromatin structure during breast cell aging may play a crucial role in regulating gene activity. To understand if these age-related molecular changes in mice translate to human breast cancer risk, Anczukow and Ucar, along with their teams, compared their data to genetic profiles of human breast tumors. They found striking similarities between the age-related molecular signatures in mice and patterns observed in human breast cancers. This suggests that the aging breast microenvironment directly influences cancer risk and could provide valuable warning signs. Brittany Angarola, Ph.D., an associate research scientist at JAX and co-first author of the study, expressed excitement about these overlapping pathways. 'It suggests that aging-related shifts in healthy tissue might create a more cancer-friendly environment before tumors even form,' she said.This open-access atlas offers a crucial resource for scientists worldwide to explore the intricate relationship between aging and cancer risk. The dataset enables researchers to identify potential biomarkers for early detection and develop strategies for prevention and treatment.'This study not only advances our understanding of aging and cancer but also lays the groundwork for future research into interventions that could reduce cancer risk in aging populations,' Anczukow concluded. 'It provides us with a powerful tool to help cancer patients everywhere.'This research was supported by The JAX Cancer Center, The JAX Center for Aging Research, The V Foundation, The Tallen-Kane Foundation, The Scott R. MacKenzie Foundation, and The Hevolution Foundation
AGING CANCER BREAST CANCER MOLECULAR BIOLOGY GENETICS EPIGENETICS BIOMARKERS EARLY DETECTION
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