Academic Journal
Lysine-specific demethylase 1 (LSD1) suppresses cellular senescence by riboflavin uptake-dependent demethylation activity
| Title: | Lysine-specific demethylase 1 (LSD1) suppresses cellular senescence by riboflavin uptake-dependent demethylation activity |
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| Authors: | Taiichi Osumi, Taiki Nagano, Tetsushi Iwasaki, Jotaro Nakanishi, Kazuyuki Miyazawa, Shinji Kamada |
| Source: | Scientific Reports, Vol 15, Iss 1, Pp 1-13 (2025) |
| Publisher Information: | Nature Portfolio, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | LSD1, Demethylation, Cellular senescence, Riboflavin, Flavin adenine dinucleotide (FAD), DNA damage, Medicine, Science |
| More Details: | Abstract Cellular senescence is defined as a permanent proliferation arrest caused by various stresses, including DNA damage. We have recently identified the riboflavin transporter SLC52A1, whose expression is increased in response to senescence-inducing stimuli. Interestingly, increased expression of SLC52A1 suppresses cellular senescence through the uptake of riboflavin and an increase in intracellular flavin adenine dinucleotide (FAD), an enzyme cofactor synthesized from riboflavin. However, how FAD suppresses cellular senescence has not been fully elucidated. Therefore, in this study, we focused on lysine-specific demethylase 1 (LSD1), which uses FAD as a cofactor. First, we found that LSD1 inhibition promoted DNA damage-induced cellular senescence, whereas ectopic expression of LSD1 suppressed cellular senescence, suggesting that LSD1 suppresses senescence. In addition, the demethylation activity of LSD1 against histone H3 and p53 was increased by senescence-inducing stress in a riboflavin uptake-dependent manner. Furthermore, it was revealed that the LSD1 demethylation activity was required for suppression of pro-senescence genes Sirtuin-4 and p21 whose expression is modified by methylation status of histone H3 and possibly p53, respectively. Collectively, these results suggest that the FAD increase by senescence-inducing stress leads to LSD1-mediated demethylation of histone H3 and p53, which results in the suppression of pro-senescence genes to inhibit senescence induction. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-025-91004-0 |
| Access URL: | https://doaj.org/article/6ba6ab05044941d49471ce30ab7f0a7a |
| Accession Number: | edsdoj.6ba6ab05044941d49471ce30ab7f0a7a |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-025-91004-0 |
| Published in: | Scientific Reports |
| Language: | English |