Midkine as a driver of age-related changes and increase in mammary tumorigenesis.

Pengze Yan, Ernesto Rojas Jimenez, Zheqi Li, Triet Bui, Marco Seehawer, Jun Nishida, Pierre Foidart, Laura E Stevens, Yingtian Xie, Miguel Munoz Gomez, So Yeon Park, Henry W Long, Kornelia Polyak

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. · pubmed

Paper

Abstract

Aging is a pivotal risk factor for cancer, yet the underlying mechanisms remain poorly defined. Here, we explore age-related changes in the rat mammary gland by single-cell multiomics. Our findings include increased epithelial proliferation, loss of luminal identity, and decreased naive B and T cells with age. We discover a luminal progenitor population unique to old rats with profiles reflecting precancerous changes and identify midkine (Mdk) as a gene upregulated with age and a regulator of age-related luminal progenitors. Midkine treatment of young rats mimics age-related changes via activating PI3K-AKT-SREBF1 pathway and promotes nitroso-N-methylurea-induced mammary tumorigenesis. Midkine levels increase with age in human blood and mammary epithelium, and higher MDK in normal breast tissue is associated with higher breast cancer risk in younger women. Our findings reveal a link between aging and susceptibility to tumor initiation and identify midkine as a mediator of age-dependent increase in breast tumorigenesis.

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Research summary

The paper investigates the role of midkine in age-related changes and its association with increased mammary tumorigenesis, linking aging mechanisms to cancer susceptibility. While it provides solid research on the relationship between aging and cancer, it primarily focuses on a specific pathway rather than addressing broader root causes of aging or lifespan extension. Thus, it contributes to the understanding of age-related diseases but has limited implications for longevity research as a whole.

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