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Updated: Nov 8, 2025

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Senescent cell removal via JAG1-NOTCH1 signalling in the epidermis

Hisashi Yoshioka1, Takaaki Yamada1,2,3, Seiji Hasegawa1,3,4

  • 1Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Japan.

Experimental Dermatology
|April 23, 2021
PubMed

Insights

Senescent cells accumulate with age due to decreased Notch signaling. This study reveals Notch signaling

Area of Science:

  • Dermatology and aging research
  • Cellular senescence and tissue homeostasis
  • Molecular signaling pathways in skin biology

Background:

  • Senescent cells accumulate in tissues with age, contributing to aging.
  • Epidermal senescent cells are implicated in age-related skin changes.
  • The mechanisms for removing senescent cells and their age-related decline are unclear.

Purpose of the Study:

  • To investigate the role of Notch signaling in the removal of senescent epidermal cells.
  • To determine if age-related changes in Notch signaling affect senescent cell clearance.

Main Methods:

  • Analysis of Notch1 receptor and JAG1 ligand expression in human epidermis from young and old subjects.
  • In vitro 3D reconstruction of human epidermis using normal and UVB-induced senescent cells.
  • Assessment of senescent cell depletion using JAG1 knockdown and Notch signaling inhibitors.

Main Results:

  • Notch1 receptor is upregulated in p16INK4a-positive senescent cells.
  • JAG1 ligand expression decreases in aged human epidermis.
  • Senescent cells are preferentially removed from the basal layer in vitro, a process inhibited by JAG1 knockdown or Notch inhibition.

Conclusions:

  • Notch signaling plays a role in the preferential removal of senescent epidermal cells.
  • Age-related decrease in JAG1 expression may impair Notch signaling, leading to senescent cell accumulation.
  • Targeting Notch signaling could offer strategies to manage age-related senescent cell accumulation in the skin.
Keywords:
3D reconstructed epidermisNotch signallingcell competitioncellular senescenceepidermis

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