Inducing cellular senescence in vitro by using genetically encoded photosensitizers
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Updated: Mar 13, 2026
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Nadezhda V Petrova1, Artem V Luzhin1, Ekaterina O Serebrovskaya2
1Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Abstract:
Cellular senescence, a form of cell cycle arrest, is one of the cellular responses to different types of exogenous and endogenous damage. The senescence phenotype can be induced in vitro by oncogene overexpression and/or DNA damage. Recently, we have reported a novel mechanism of cellular senescence induction by mild genotoxic stress. Specifically, we have shown that the formation of a small number of DNA lesions in normal and cancer cells during S phase leads to cellular senescence-like arrest within the same cell cycle. Here, based on this mechanism, we suggest an approach to remotely induce premature senescence in human cell cultures using short-term light irradiation. We used the genetically encoded photosensitizers, tandem KillerRed and miniSOG, targeted to chromatin by fusion to core histone H2B to induce moderate levels of DNA damage by light in S phase cells. We showed that the cells that express the H2B-fused photosensitizers acquire a senescence phenotype upon illumination with the appropriate light source. Furthermore, we demonstrated that both chromatin-targeted tandem KillerRed (produces O2¯) and miniSOG (produces 1O2) induce single-stranded DNA breaks upon light illumination. Interestingly, miniSOG was also able to induce double-stranded DNA breaks.
Insights
Researchers developed a novel method to remotely induce cellular senescence, a cell cycle arrest, using light-activated proteins. This technique triggers DNA damage in S phase cells, leading to premature senescence in human cell cultures.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cellular senescence is a crucial cell cycle arrest mechanism responding to DNA damage.
- Previous research identified mild genotoxic stress as a trigger for cellular senescence.
- A novel mechanism involves DNA lesions during S phase inducing senescence within the same cell cycle.
Purpose of the Study:
- To propose a remote method for inducing premature cellular senescence in human cell cultures.
- To utilize light-activated photosensitizers for targeted DNA damage induction.
- To investigate the efficacy of genetically encoded photosensitizers in triggering senescence.
Main Methods:
- Genetically encoded photosensitizers, tandem KillerRed and miniSOG, were fused to histone H2B for chromatin targeting.
- These fusion proteins were expressed in human cell cultures.
- Short-term light irradiation was used to activate photosensitizers and induce DNA damage in S phase cells.
Main Results:
- Cells expressing H2B-fused photosensitizers exhibited a senescence phenotype upon light illumination.
- Both tandem KillerRed and miniSOG induced single-stranded DNA breaks after light exposure.
- MiniSOG demonstrated the capability to induce double-stranded DNA breaks.
Conclusions:
- Light-activated, chromatin-targeted photosensitizers offer a remote method to induce premature cellular senescence.
- This approach leverages light-induced DNA damage to control cell cycle arrest.
- The study provides a novel tool for investigating senescence in cellular and potentially in vivo models.
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