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Updated: Jul 19, 2025

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Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging

Yuli Hou1, Qiao Song1, Yaqi Wang1

  • 1Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.

Aging Cell
|August 8, 2023
PubMed

Insights

Krüppel-like factor 14 (KLF14) suppresses cellular senescence and aging. Lower KLF14 levels accelerate aging, while KLF14 activation, potentially via perhexiline, delays aging and related diseases by boosting POLD1 expression.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Cellular Biology

Background:

  • Aging is a significant risk factor for numerous diseases.
  • Understanding the molecular mechanisms of aging is crucial for developing interventions.
  • Krüppel-like factor 14 (KLF14) has been investigated for its role in aging processes.

Purpose of the Study:

  • To investigate the role of Krüppel-like factor 14 (KLF14) as a suppressor of cellular senescence and aging.
  • To elucidate the molecular mechanisms by which KLF14 influences aging.
  • To explore therapeutic potential of KLF14 modulation in aging.

Main Methods:

  • Measured KLF14 levels in human lymphocytes and aging mouse tissues.
  • Conducted in vitro and in vivo experiments using KLF14-deficient and overexpressing cells and mice.
  • Utilized molecular techniques to assess KLF14's effect on POLD1 promoter activity and expression.
  • Administered perhexiline, a KLF14 agonist, to senescence-accelerated mice.

Main Results:

  • KLF14 levels decreased with aging in humans and mice.
  • KLF14 deficiency accelerated cellular senescence and aging pathologies in mice.
  • KLF14 overexpression attenuated cellular senescence.
  • KLF14 positively regulated POLD1 expression by binding to its promoter.
  • POLD1 expression alleviated KLF14 downregulation-mediated senescence.
  • Perhexiline delayed senescence and aging pathologies by enhancing KLF14's transcriptional activation of POLD1.

Conclusions:

  • KLF14 acts as a critical suppressor of cellular senescence and aging.
  • KLF14 delays aging by upregulating POLD1 expression.
  • Activation of KLF14, potentially through compounds like perhexiline, may offer a therapeutic strategy to delay aging and associated diseases.
Keywords:
KLF14POLD1agingcellular senescencetranscriptional regulation

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