SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation.
Senescent cells develop a pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). As many SASP components affect surrounding cells and alter their microenvironment, SASP may be a key phenomenon in linking cellular senesence with individual aging and age-related disease...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4312089?pdf=render |
| _version_ | 1818949071459581952 |
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| author | Tomohisa Hayakawa Mika Iwai Satoshi Aoki Koichi Takimoto Mitsuo Maruyama Wakako Maruyama Noboru Motoyama |
| author_facet | Tomohisa Hayakawa Mika Iwai Satoshi Aoki Koichi Takimoto Mitsuo Maruyama Wakako Maruyama Noboru Motoyama |
| author_sort | Tomohisa Hayakawa |
| collection | DOAJ |
| description | Senescent cells develop a pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). As many SASP components affect surrounding cells and alter their microenvironment, SASP may be a key phenomenon in linking cellular senesence with individual aging and age-related diseases. We herein demonstrated that the expression of Sirtuin1 (SIRT1) was decreased and the expression of SASP components was reciprocally increased during cellular senescence. The mRNAs and proteins of SASP components, such as IL-6 and IL-8, quickly accumulated in SIRT1-depleted cells, and the levels of these factors were also higher than those in control cells, indicating that SIRT1 negatively regulated the expression of SASP factors at the transcriptional level. SIRT1 bound to the promoter regions of IL-8 and IL-6, but dissociated from them during cellular senescence. The acetylation of Histone H3 (K9) and H4 (K16) of the IL-8 and IL-6 promoter regions gradually increased during cellular senescence. In SIRT1-depleted cells, the acetylation levels of these regions were already higher than those in control cells in the pre-senescent stage. Moreover, these acetylation levels in SIRT1-depleted cells were significantly higher than those in control cells during cellular senescence. These results suggest that SIRT1 repressed the expression of SASP factors through the deacetylation of histones in their promoter regions. |
| first_indexed | 2024-12-20T08:56:52Z |
| format | Article |
| id | doaj.art-0bc1fcab8b4746579c28d88ca7a70f90 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T08:56:52Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0bc1fcab8b4746579c28d88ca7a70f902022-12-21T19:45:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011648010.1371/journal.pone.0116480SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation.Tomohisa HayakawaMika IwaiSatoshi AokiKoichi TakimotoMitsuo MaruyamaWakako MaruyamaNoboru MotoyamaSenescent cells develop a pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). As many SASP components affect surrounding cells and alter their microenvironment, SASP may be a key phenomenon in linking cellular senesence with individual aging and age-related diseases. We herein demonstrated that the expression of Sirtuin1 (SIRT1) was decreased and the expression of SASP components was reciprocally increased during cellular senescence. The mRNAs and proteins of SASP components, such as IL-6 and IL-8, quickly accumulated in SIRT1-depleted cells, and the levels of these factors were also higher than those in control cells, indicating that SIRT1 negatively regulated the expression of SASP factors at the transcriptional level. SIRT1 bound to the promoter regions of IL-8 and IL-6, but dissociated from them during cellular senescence. The acetylation of Histone H3 (K9) and H4 (K16) of the IL-8 and IL-6 promoter regions gradually increased during cellular senescence. In SIRT1-depleted cells, the acetylation levels of these regions were already higher than those in control cells in the pre-senescent stage. Moreover, these acetylation levels in SIRT1-depleted cells were significantly higher than those in control cells during cellular senescence. These results suggest that SIRT1 repressed the expression of SASP factors through the deacetylation of histones in their promoter regions.http://europepmc.org/articles/PMC4312089?pdf=render |
| spellingShingle | Tomohisa Hayakawa Mika Iwai Satoshi Aoki Koichi Takimoto Mitsuo Maruyama Wakako Maruyama Noboru Motoyama SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. PLoS ONE |
| title | SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. |
| title_full | SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. |
| title_fullStr | SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. |
| title_full_unstemmed | SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. |
| title_short | SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. |
| title_sort | sirt1 suppresses the senescence associated secretory phenotype through epigenetic gene regulation |
| url | http://europepmc.org/articles/PMC4312089?pdf=render |
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