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Updated: Jan 7, 2026

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
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Multi-Omics Analysis Reveals Photodynamic Therapy Ameliorating Skin Photoaging by Improving Cellular Senescence

Yu Yan1, Qihang Chang1, Yun Wu1

  • 1Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.

Aging Cell
|December 28, 2025
PubMed

Insights

5-aminolevulinic acid photodynamic therapy (ALA-PDT) reverses skin aging by activating beneficial stress responses. This treatment reduces cellular senescence and citrate levels, offering a new metabolic approach for age-related skin conditions.

Area of Science:

  • Dermatology
  • Biochemistry
  • Molecular Biology

Background:

  • Clinical evidence suggests 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is effective against photoaging.
  • The precise mechanism behind ALA-PDT's rejuvenating effects, especially its generation of reactive oxygen species (ROS), remains unclear.

Purpose of the Study:

  • To elucidate the paradoxical mechanism of ALA-PDT in combating photoaging.
  • To investigate ALA-PDT's impact on cellular senescence, mitochondrial function, and metabolism in UV-induced skin aging.

Main Methods:

  • Utilized a multi-omics approach (transcriptomics, proteomics, metabolomics) on skin biopsies from a UVR-induced hairless mouse model.
  • Conducted in vitro experiments on UV-stressed fibroblasts to assess ALA-PDT's protective effects.
  • Assessed mitochondrial function and citrate levels pre- and post-treatment.

Main Results:

  • ALA-PDT significantly improved photoaging phenotypes in mice, enhancing epidermal structure, extracellular matrix, and immune response.
  • Identified ALA-PDT-induced mitohormesis and tricarboxylic acid cycle reprogramming, characterized by reduced intracellular citrate.
  • In vitro, low-dose ALA-PDT decreased senescence markers and citrate in stressed fibroblasts, with effects dependent on ROS-mediated mitohormesis.

Conclusions:

  • Low-dose ALA-PDT alleviates photoaging by mitigating cellular senescence through ROS-dependent mitohormesis and citrate reduction.
  • This study reveals a novel metabolic intervention strategy for managing age-related skin disorders.
  • ALA-PDT's anti-photoaging effects are linked to its ability to induce beneficial mitohormetic signaling pathways.
Keywords:
ALA‐PDTcellular senescencemitohormesisphotoagingreactive oxygen species

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