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Free Radic Biol Med ; 221: 98-110, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38754743

ABSTRACT

Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 µM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Longevity , Oxidative Stress , Perylene , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species , Transcription Factors , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/genetics , Oxidative Stress/drug effects , Longevity/drug effects , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Perylene/analogs & derivatives , Perylene/pharmacology , Anthracenes/pharmacology , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Gene Expression Regulation/drug effects , Light , Acetylcysteine/pharmacology
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