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Inflamm-aging of the stem cell niche: Breast cancer as a paradigmatic example

Breakdown of the multi-shell cytokine network fuels cancer in aged people

Authors

  • Massimiliano Bonafè,

    1. Department of Experimental Pathology, University of Bologna, Italy
    2. CRBA, Center for Applied Biomedical Research, Policlinico S.Orsola Malpighi, University of Bologna, Italy
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  • Gianluca Storci,

    1. Department of Experimental Pathology, University of Bologna, Italy
    2. CRBA, Center for Applied Biomedical Research, Policlinico S.Orsola Malpighi, University of Bologna, Italy
    3. Institute of Oncology and Hematology “L. & A Seragnoli”, Policlinico S.Orsola Malpighi, University of Bologna, Italy
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  • Claudio Franceschi

    Corresponding author
    1. Department of Experimental Pathology, University of Bologna, Italy
    • Department of Experimental Pathology, University of Bologna, Italy.
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Abstract

Inflamm-aging is a relatively new terminology used to describe the age-related increase in the systemic pro-inflammatory status of humans. Here, we represent inflamm-aging as a breakdown in the multi-shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro-inflammatory cytokine over-expressing cells due to the accumulation of DNA damage. Inflamm-aging self-propagates owing to the capability of pro-inflammatory cytokines to ignite the DNA-damage response in other cells surrounding DNA-damaged cells. Macrophages, the major cellular player in inflamm-aging, amplify the phenomenon, by broadcasting pro-inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm-aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship.

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