The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases
Open accessAbstract
"Cellular senescence" is a state in which cells undergo irreversible cell cycle arrest in response to a variety of cellular stresses. Once cells senesce, they are strongly resistant to any mitogens, including oncogenic stimuli. Therefore, cellular senescence has been assumed to be a potent anticancer mechanism. Although irreversible cell-cycle arrest is traditionally considered the major characteristic of senescent cells, recent studies have revealed some additional functions. Most noteworthy is the increased secretion of various secretory proteins, such as inflammatory cytokines, chemokines, growth factors, and MMPs, into the surrounding extracellular fluid. These newly recognized senescent phenotypes, termed senescence-associated secretory phenotypes (SASPs), reportedly contribute to tumor suppression, wound healing, embryonic development, and even tumorigenesis promotion. Thus, SASPs appear to be beneficial or deleterious, depending on the biological context. As senescent cells are known to accumulate during the aging process in vivo, it is quite possible that their accumulation in aged tissues promotes age-associated functional decline and various diseases, including cancers, at least to some extent. Here, we focus on and discuss the functional and regulatory network of SASPs toward opening up new possibilities for controlling aging and aging-associated diseases.
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“Senescent cells accumulate with age in the dermis and epidermis, which can be accelerated by various harmful factors, such as DNA-damaging agents (eg, x-rays, ultraviolet radiation, and cigarette smoke) and mitochondrial dysfunction.56”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [56]
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1 retracted
Kaur, A., Webster, M. R., Marchbank, K., Behera, R., Ndoye, A., Kugel, C. H., Dang, V. M., Appleton, J., O’Connell, M. P., Cheng, P., et al. (2016) · Nature · doi:10.1038/nature17392 · Cited by 398
RetractedThe serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
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Items 301–321 of 321
Ahmed, F., & Khanam, R. (2023) · Springer eBooks · doi:10.1007/978-981-99-7652-2_20
Genome Instability in Chemotherapy-Induced Senescence
Yadav, V., & Jahan, K. (2025) · Genetics. · doi:10.5772/intechopen.1010588
Li, K., Li, Y., Yu, Y., Ding, J., Huang, H., Chu, C., Hu, L., Yu, Y., Cao, Y., Xu, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14173917
Zhang, S., Du, J., Aikeremu, D., Ma, Z., & Wang, H. (2026) · Experimental Gerontology · doi:10.1016/j.exger.2026.113025
Devlin, P. J., Khan, R., Do, T. H., West, B. E., Korf, J. M., Guzman, G. U., Tan, C., Ahn, J., Flores, R., Maniskas, M. E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.12.699107
Zhang, S., Deng, S.-S., Dai, K., Liu, Y., Wang, J., & Liu, C.-S. (2026) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.11.039
“…senescence-associated β -galactosidase activity, loss of nuclear high mobility group box 1 [19], and the development of a senescence-associated secretory phenotype (SASP) [20 – 26], which encompasses a spectrum of inflammatory cytokines, chemokines, and prostaglandin-related oxylipins [27].”
Lemey, C. (2017) · theses.fr (ABES) · doi:10.70675/14dca0fcze537z4da0z9184z9b59c260ea88
Kychygina, G. (2019) · theses.fr (ABES) · doi:10.70675/257216a4zfec4z40ccza35bz81fab5ab7e1e
The role of Activin signaling pathway in the initiation and progression of pancreatic cancer
Zhao, Y. (2019) · theses.fr (ABES) · doi:10.70675/17612dbdz6d94z4563z86a3z6d1e91b34f9b
Soysouvanh, F. (2019) · theses.fr (ABES) · doi:10.70675/3890835fzb557z430aza571z697de58045dd
Radiosensibilité des sous-populations lymphocytaires T et sénescence radio-induite
Nguyen, H. Q. (2019) · theses.fr (ABES) · doi:10.70675/6c94f1c0z17d2z42cazb118z8c7e07496c2b
Impact of aging on cardiac mesenchymal stromal cells
Martini, H. (2019) · theses.fr (ABES) · doi:10.70675/bb7ddcb3z0b6az4c39za6eczc94e0563f0a3
Anti-Aging the Immune System: Hype or Hope? A Mechanistic Review
Ilyas, A. (2026) · Premier Journal of Immunology · doi:10.70389/pji.100011
Repeated head impacts establish a senescent cranial bone marrow niche that impairs brain metabolism
Devlin, P., Khan, R., Do, T., West, B. E., Korf, J. M., Guzman, G. U., Ahn, J., Saltzman, A. B., Jain, A., Tan, C., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03846-8
“IL-6 is one of the core SASP factors most commonly observed across cell types and models [58, 59].”
Dong, H., Shu, C., Liu, R., Zhao, M., Zhang, K., Qu, Z., Wang, L., Fan, J., & Ye, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1863063 · Cited by 1
“Senescent cells can in fl uence neighboring cells by secreting a senescence-associated secretory phenotype (SASP) comprising pro-in fl ammatory mediators (7).”
Sarcopenia and sepsis fuel a self-perpetuating cycle of immunometabolism decline
Gutman, E. G., Muniz‐Santos, R., da Silva, A. M., Costa, G. L. A., da Cunha, C. M. C., de Moraes, B. P. T., & Gonçalves-de-Albuquerque, C. F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1867909
“…cells resident in skeletal muscle that accumulate with age, characterized by the overexpression of pro-in fl ammatory mediators such as Interleukin-1 b (IL-1 b ), IL-6, IL-8, tumor necrosis factor-a (TNF-a ), and Interferon-g (IFN-g ), thereby promoting a pro-in fl ammatory environment (41).”
Choi, Y. H. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101836
Zhang, Y., Wang, Y., Shao, H., Guo, X., Xu, P., 李彦郎, Jia, J., Dong, F., Hu, J.-M., & Yang, L. (2026) · Natural Products and Bioprospecting · doi:10.1007/s13659-026-00642-y
The Effects Of Chronıc Inflammatıon On Agıng And The Characterıstıcs Of The NLRP3 Inflammasome
Başaran, A. (2026) · Uluslararası Sağlık Bilimlerinde Disiplinler Arası Etkileşim Dergisi · doi:10.65349/atub7085
Targeting senescence-mediated immune resistance for enhanced tumor immunotherapy
Chen, S., Su, J., Jin, A., Liu, C., Zhang, P., Xu, Z., Pan, J., Lai, Y., & Yu, H. (2026) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2026.26
Nadholta, P., Volety, I., & Shukla, D. (2026) · Virology · doi:10.1016/j.virol.2026.111113
Metadata
- Authors
- Watanabe, S., Kawamoto, S., Ohtani, N., & Hara, E.
- Affiliations
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Tokyo University of Science (JP)
- Japanese Foundation For Cancer Research (JP)
- Corresponding author
- Watanabe, Sugiko
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2017-04
- Volume
- 108
- Issue
- 4
- Pages
- 563-569
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC5406532
- OpenAlex
- W2587299332
- Cited by
- 321
- References
- 88
- Citations by year
- 2026: 22 · 2025: 27 · 2024: 29 · 2023: 39 · 2022: 33 · 2021: 41 · 2020: 47 · 2019: 47 · 2018: 33 · 2017: 3
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Astellas Foundation for Research on Metabolic Disorders
- Naito Foundation
- Japan Agency for Medical Research and Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- senescence-associated secretory phenotype, cellular senescence, aging, senolytics, secreted proteins, inflammatory cytokines, chemokines, matrix metalloproteinases, tumor suppression, carcinogenesis, cell cycle arrest, therapeutic target
- MeSH terms
- Aging, Animals, Cell Transformation, Neoplastic, Disease, Humans, Neoplasms, Phenotype, Cellular Senescence, Secretory Pathway, Cell Cycle Checkpoints
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