The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues
Cellular senescence and cellular reprogramming represent two fundamentally intertwined processes that profoundly influence aging and cancer. This paper explores how the permanent cell-cycle arrest of senescent cells and the identity-resetting capacity of reprogramming jointly shape biological outcom...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1593096/full |
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| author | Fuan Ding Ying Yu Jiangqi Zhao Shibo Wei Yan Zhang Jung Ho Han Zhuo Li Hong-Bo Jiang Dongryeol Ryu Minkyoung Cho Sung-Jin Bae Wonyoung Park Wonyoung Park Ki-Tae Ha Ki-Tae Ha Bo Gao |
| author_facet | Fuan Ding Ying Yu Jiangqi Zhao Shibo Wei Yan Zhang Jung Ho Han Zhuo Li Hong-Bo Jiang Dongryeol Ryu Minkyoung Cho Sung-Jin Bae Wonyoung Park Wonyoung Park Ki-Tae Ha Ki-Tae Ha Bo Gao |
| author_sort | Fuan Ding |
| collection | DOAJ |
| description | Cellular senescence and cellular reprogramming represent two fundamentally intertwined processes that profoundly influence aging and cancer. This paper explores how the permanent cell-cycle arrest of senescent cells and the identity-resetting capacity of reprogramming jointly shape biological outcomes in later life and tumor development. We synthesize recent findings to show that senescent cells, while halting the proliferation of damaged cells, can paradoxically promote tissue dysfunction and malignancy via their secretory phenotype. Conversely, induced reprogramming of somatic cells—exemplified by Yamanaka factors—resets cellular age and epigenetic marks, offering a potential to rejuvenate aged cells. Key findings highlight shared mechanisms (e.g., DNA damage responses and epigenetic remodeling) and bidirectional crosstalk between these processes: senescence signals can facilitate neighboring cell plasticity, whereas reprogramming attempts can trigger intrinsic senescence programs as a barrier. In aging tissues, transient (partial) reprogramming has been shown to erase senescence markers and restore cell function without inducing tumorigenesis, underlining a novel strategy to combat age-related degeneration. In cancer, we discuss how therapy-induced senescence of tumor cells may induce stem-cell-like traits in some cells and drive relapse, revealing a delicate balance between tumor suppression and tumor promotion. Understanding the interplay between senescence and reprogramming is crucial for developing innovative therapies. By targeting the senescence–reprogramming axis–for instance, via senolytic drugs, SASP inhibitors, or safe reprogramming techniques–there is significant therapeutic potential to ameliorate aging-related diseases and improve cancer treatment. Our findings underscore that carefully modulating cellular senescence and rejuvenation processes could pave the way for novel regenerative and anti-cancer strategies. |
| format | Article |
| id | doaj-art-69e786cb15bf47bd998a947219428aa0 |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-69e786cb15bf47bd998a947219428aa02025-08-20T02:29:46ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-04-011310.3389/fcell.2025.15930961593096The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenuesFuan Ding0Ying Yu1Jiangqi Zhao2Shibo Wei3Yan Zhang4Jung Ho Han5Zhuo Li6Hong-Bo Jiang7Dongryeol Ryu8Minkyoung Cho9Sung-Jin Bae10Wonyoung Park11Wonyoung Park12Ki-Tae Ha13Ki-Tae Ha14Bo Gao15Department of Vascular Surgery, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Surgery, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Dermatology, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of KoreaDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of KoreaDepartment of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Dermatology, Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, Shandong, ChinaDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of KoreaDepartment of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Republic of KoreaDepartment of Molecular Biology and Immunology, Kosin University College of Medicine, Busan, Republic of Korea0Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea1Research Institute for Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea0Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea1Research Institute for Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of KoreaDepartment of Vascular Surgery, The Second Hospital of Jilin University, Changchun, ChinaCellular senescence and cellular reprogramming represent two fundamentally intertwined processes that profoundly influence aging and cancer. This paper explores how the permanent cell-cycle arrest of senescent cells and the identity-resetting capacity of reprogramming jointly shape biological outcomes in later life and tumor development. We synthesize recent findings to show that senescent cells, while halting the proliferation of damaged cells, can paradoxically promote tissue dysfunction and malignancy via their secretory phenotype. Conversely, induced reprogramming of somatic cells—exemplified by Yamanaka factors—resets cellular age and epigenetic marks, offering a potential to rejuvenate aged cells. Key findings highlight shared mechanisms (e.g., DNA damage responses and epigenetic remodeling) and bidirectional crosstalk between these processes: senescence signals can facilitate neighboring cell plasticity, whereas reprogramming attempts can trigger intrinsic senescence programs as a barrier. In aging tissues, transient (partial) reprogramming has been shown to erase senescence markers and restore cell function without inducing tumorigenesis, underlining a novel strategy to combat age-related degeneration. In cancer, we discuss how therapy-induced senescence of tumor cells may induce stem-cell-like traits in some cells and drive relapse, revealing a delicate balance between tumor suppression and tumor promotion. Understanding the interplay between senescence and reprogramming is crucial for developing innovative therapies. By targeting the senescence–reprogramming axis–for instance, via senolytic drugs, SASP inhibitors, or safe reprogramming techniques–there is significant therapeutic potential to ameliorate aging-related diseases and improve cancer treatment. Our findings underscore that carefully modulating cellular senescence and rejuvenation processes could pave the way for novel regenerative and anti-cancer strategies.https://www.frontiersin.org/articles/10.3389/fcell.2025.1593096/fullagingcancercellular senescencereprogrammingtumor progression |
| spellingShingle | Fuan Ding Ying Yu Jiangqi Zhao Shibo Wei Yan Zhang Jung Ho Han Zhuo Li Hong-Bo Jiang Dongryeol Ryu Minkyoung Cho Sung-Jin Bae Wonyoung Park Wonyoung Park Ki-Tae Ha Ki-Tae Ha Bo Gao The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues Frontiers in Cell and Developmental Biology aging cancer cellular senescence reprogramming tumor progression |
| title | The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues |
| title_full | The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues |
| title_fullStr | The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues |
| title_full_unstemmed | The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues |
| title_short | The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues |
| title_sort | interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues |
| topic | aging cancer cellular senescence reprogramming tumor progression |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1593096/full |
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