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Mid-old cells are a potential target for anti-aging interventions in the elderly

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Listed:
  • Young Hwa Kim

    (Ajou University Medical Center)

  • Young-Kyoung Lee

    (Ajou University Medical Center
    Ajou University School of Medicine)

  • Soon Sang Park

    (Ajou University Medical Center
    Ajou University School of Medicine
    Ajou University Graduate School of Medicine)

  • So Hyun Park

    (Ajou University School of Medicine)

  • So Yeong Eom

    (Ajou University Medical Center
    Ajou University Graduate School of Medicine
    Ajou University School of Medicine)

  • Young-Sam Lee

    (Daegu Gyeongbuk Institute of Science & Technology)

  • Wonhee John Lee

    (Daegu Gyeongbuk Institute of Science & Technology)

  • Juhee Jang

    (Daegu Gyeongbuk Institute of Science & Technology)

  • Daeha Seo

    (Daegu Gyeongbuk Institute of Science & Technology)

  • Hee Young Kang

    (Ajou University Medical Center
    Ajou University School of Medicine)

  • Jin Cheol Kim

    (Ajou University Medical Center
    Ajou University School of Medicine)

  • Su Bin Lim

    (Ajou University Medical Center
    Ajou University School of Medicine
    Ajou University Graduate School of Medicine)

  • Gyesoon Yoon

    (Ajou University Medical Center
    Ajou University School of Medicine
    Ajou University Graduate School of Medicine)

  • Hong Seok Kim

    (College of Medicine, Inha University)

  • Jang-Hee Kim

    (Ajou University Medical Center
    Ajou University School of Medicine)

  • Tae Jun Park

    (Ajou University Medical Center
    Ajou University School of Medicine
    Ajou University Graduate School of Medicine)

Abstract

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Suggested Citation

  • Young Hwa Kim & Young-Kyoung Lee & Soon Sang Park & So Hyun Park & So Yeong Eom & Young-Sam Lee & Wonhee John Lee & Juhee Jang & Daeha Seo & Hee Young Kang & Jin Cheol Kim & Su Bin Lim & Gyesoon Yoon , 2023. "Mid-old cells are a potential target for anti-aging interventions in the elderly," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43491-w
    DOI: 10.1038/s41467-023-43491-w
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    1. Darren J. Baker & Tobias Wijshake & Tamar Tchkonia & Nathan K. LeBrasseur & Bennett G. Childs & Bart van de Sluis & James L. Kirkland & Jan M. van Deursen, 2011. "Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders," Nature, Nature, vol. 479(7372), pages 232-236, November.
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