New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation
Senescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5857 |
| _version_ | 1797611194574438400 |
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| author | Kento Takaya Toru Asou Kazuo Kishi |
| author_facet | Kento Takaya Toru Asou Kazuo Kishi |
| author_sort | Kento Takaya |
| collection | DOAJ |
| description | Senescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker expressed on senescent dermal fibroblasts, and investigated a novel senolysis approach using a monoclonal antibody against this antigen and a secondary antibody conjugated with the cytotoxic drug pyrrolobenzodiazepine. Observations using fluorescently labeled antibodies revealed that ApoD functions as a surface marker of senescent cells and that the antibody is taken up and internalized only by such cells. The concurrent administration of the antibody with the PBD-conjugated secondary antibody specifically eliminated only senescent cells without harming young cells. The antibody–drug conjugate treatment of aging mice combined with the administration of antibodies reduced the number of senescent cells in the dermis of mice and improved the senescent skin phenotype. These results provide a proof-of-principle evaluation of a novel approach to specifically eliminate senescent cells using antibody–drug conjugates against senescent cell marker proteins. This approach is a potential candidate for clinical applications to treat pathological skin aging and related diseases via the removal of senescent cells. |
| first_indexed | 2024-03-11T06:25:23Z |
| format | Article |
| id | doaj.art-bf1fcb8025a544aba3e5a27fd457762c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:25:23Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bf1fcb8025a544aba3e5a27fd457762c2023-11-17T11:40:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246585710.3390/ijms24065857New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin RejuvenationKento Takaya0Toru Asou1Kazuo Kishi2Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo 160-8582, JapanSenescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker expressed on senescent dermal fibroblasts, and investigated a novel senolysis approach using a monoclonal antibody against this antigen and a secondary antibody conjugated with the cytotoxic drug pyrrolobenzodiazepine. Observations using fluorescently labeled antibodies revealed that ApoD functions as a surface marker of senescent cells and that the antibody is taken up and internalized only by such cells. The concurrent administration of the antibody with the PBD-conjugated secondary antibody specifically eliminated only senescent cells without harming young cells. The antibody–drug conjugate treatment of aging mice combined with the administration of antibodies reduced the number of senescent cells in the dermis of mice and improved the senescent skin phenotype. These results provide a proof-of-principle evaluation of a novel approach to specifically eliminate senescent cells using antibody–drug conjugates against senescent cell marker proteins. This approach is a potential candidate for clinical applications to treat pathological skin aging and related diseases via the removal of senescent cells.https://www.mdpi.com/1422-0067/24/6/5857agingsenolysisantibody drug conjugateapolipoprotein D |
| spellingShingle | Kento Takaya Toru Asou Kazuo Kishi New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation International Journal of Molecular Sciences aging senolysis antibody drug conjugate apolipoprotein D |
| title | New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation |
| title_full | New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation |
| title_fullStr | New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation |
| title_full_unstemmed | New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation |
| title_short | New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation |
| title_sort | new senolysis approach via antibody drug conjugate targeting of the senescent cell marker apolipoprotein d for skin rejuvenation |
| topic | aging senolysis antibody drug conjugate apolipoprotein D |
| url | https://www.mdpi.com/1422-0067/24/6/5857 |
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