Insights from In Vivo Studies of Cellular Senescence
Open accessAbstract
Cellular senescence is the dynamic process of durable cell-cycle arrest. Senescent cells remain metabolically active and often acquire a distinctive bioactive secretory phenotype. Much of our molecular understanding in senescent cell biology comes from studies using mammalian cell lines exposed to stress or extended culture periods. While less well understood mechanistically, senescence in vivo is becoming appreciated for its numerous biological implications, both in the context of beneficial processes, such as development, tumor suppression, and wound healing, and in detrimental conditions, where senescent cell accumulation has been shown to contribute to aging and age-related diseases. Importantly, clearance of senescent cells, through either genetic or pharmacological means, has been shown to not only extend the healthspan of prematurely and naturally aged mice but also attenuate pathology in mouse models of chronic disease. These observations have prompted an investigation of how and why senescent cells accumulate with aging and have renewed exploration into the characteristics of cellular senescence in vivo. Here, we highlight our molecular understanding of the dynamics that lead to a cellular arrest and how various effectors may explain the consequences of senescence in tissues. Lastly, we discuss how exploitation of strategies to eliminate senescent cells or their effects may have clinical utility.
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These findings challenge the prevalent view that senescent cells are beneficial when transiently present after acute injury, particularly in young tissue.
“These findings challenge the prevalent view that senescent cells are beneficial when transiently present after acute injury, particularly in young tissue (reviewed in refs. 28,29).”
From Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (2023) · cites this paper as [28]
The paper’s Abstract identifies wound healing as a beneficial context for cellular senescence, supporting the view the citation is offered to review. It does not specify that the benefit depends on senescent cells being transiently present after acute injury or on the tissue being young. Whether the citing authors’ findings challenge that view is their own conclusion, not a finding attributed to this review. (LLM, conf=0.82)
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Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration
Moiseeva, V., Cisneros, A., Sica, V., Deryagin, O., Lai, Y., Jung, S., Andrés, E., An, J., Segalés, J., Ortet, L., et al. (2023) · Nature · doi:10.1038/s41586-022-05535-x · Cited by 423 · see citing works
miR-21 and miR-146a: The microRNAs of inflammaging and age-related diseases
Olivieri, F., Prattichizzo, F., Giuliani, A., Matacchione, G., Rippo, M. R., Sabbatinelli, J., & Bonafè, M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101374 · Cited by 221 · see citing works
Senescent alveolar macrophages promote early-stage lung tumorigenesis
Prieto, L. I., Sturmlechner, I., Graves, S. I., Zhang, C., Goplen, N. P., Yi, E. S., Sun, J., Li, H., & Baker, D. J. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.006 · Cited by 212 · see citing works
Self-citationBasu, A. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107943 · Cited by 171 · see citing works
Senescence and the tumor-immune landscape: Implications for cancer immunotherapy
Chibaya, L., Snyder, J. T., & Ruscetti, M. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.005 · Cited by 138 · see citing works
Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential
He, Y., Xie, W., Li, H., Jin, H., Zhang, Y., & Li, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.793088 · Cited by 82 · see citing works
Calcium’s Role and Signaling in Aging Muscle, Cellular Senescence, and Mineral Interactions
Terrell, K., Choi, S., & Choi, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242317034 · Cited by 80 · see citing works
Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis
Zhang, X.-X., He, S.-H., Liang, X., Li, W., Li, T.-F., & Li, D.-F. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.728100 · Cited by 80 · see citing works
Muthamil, S., Kim, H., Jang, H., Lyu, J., Shin, U. C., Go, Y., Park, S., Lee, H. G., & Park, J. H. (2024) · Advanced Biology · doi:10.1002/adbi.202400079 · Cited by 79 · see citing works
Zhao, B., Wu, B. C., Feng, N., Zhang, X., Zhang, X., Wei, Y., & Zhang, W. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01426-4 · Cited by 65 · see citing works
Calabrò, A., Accardi, G., Aiello, A., Caruso, C., Galimberti, D., & Candore, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031792 · Cited by 56 · see citing works
Therapy-induced senescence as a component of tumor biology: Evidence from clinical cancer
Saleh, T., Bloukh, S., Hasan, M., & Shboul, S. A. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188994 · Cited by 54 · see citing works
Cellular senescence offers distinct immunological vulnerabilities in cancer
Zhou, L., Ma, B., & Ruscetti, M. A. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.11.010 · Cited by 36 · see citing works
Senolytic treatment for low back pain
Mannarino, M., Cherif, H., Darband, S. G., Martinez, O. W., Sheng, K., Cousineau, E., Lee, S., Millecamps, M., Gao, C., Gilbert, A., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr1719 · Cited by 33 · see citing works
Brain cellular senescence in mouse models of Alzheimer’s disease
Dorigatti, A. O., Riordan, R., Yu, Z., Ross, G., Wang, R., Reynolds-Lallement, N. C., Magnusson, K. R., Galván, V., & Pérez, V. (2022) · GeroScience · doi:10.1007/s11357-022-00531-5 · Cited by 32 · see citing works
Molecular Mechanisms to Target Cellular Senescence in Aging and Disease
Marcozzi, S., Beltrami, A. P., & Malavolta, M. (2022) · Cells · doi:10.3390/cells11233732 · Cited by 20 · see citing works
Cellular Senescence Is Associated with Faster Progression of Focal Segmental Glomerulosclerosis
Verzola, D., Saio, M., Picciotto, D., Viazzi, F. C., Russo, E., Cipriani, L., Carta, A., Costigliolo, F., Gaggero, G., Salvidio, G., et al. (2020) · American Journal of Nephrology · doi:10.1159/000511560 · Cited by 14 · see citing works
Loss of Dystroglycan Drives Cellular Senescence via Defective Mitosis-Mediated Genomic Instability
Jiménez-Gutiérrez, G. E., Mondragón-González, R., Soto-Ponce, L. A., Gómez-Monsivais, W. L., García‐Aguirre, I., Pacheco-Rivera, R., Suárez‐Sánchez, R., Brancaccio, A., Magaña, J. J., Perlingeiro, R. C. R., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144961 · Cited by 14 · see citing works
Immune senescence: A key player in cancer biology
Yang, Y., Fan, L., Li, M., & Wang, Z. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.12.001 · Cited by 13 · see citing works
Sui, D., Meng, X., Li, C., Tang, X., Qin, Y., Zhang, N., Ding, J., Liu, X., Deng, Y., & Song, Y. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030545 · Cited by 12 · see citing works
Ghneim, K., Sharma, A., Ribeiro, S. P., Fourati, S., Ahlers, J. D., Kulpa, D. A., Xu, X., Brehm, J. H., Talla, A., Arumugam, S. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.15.422949 · Cited by 7 · see citing works
Delayed effects of radiation in adipose tissue reflect progenitor damage and not cellular senescence
Ruggiero, A. D., Davis, M. A., Davis, A., DeStephanis, D., Williams, A. G., Vemuri, R., Fanning, K. M., Sherrill, C., Cline, J. M., Caudell, D. L., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00660-x · Cited by 6 · see citing works
Premalignant lesions and cellular senescence
Georgakopoulou, E. A., Evangelou, K., & Gorgoulis, V. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822514-1.00001-8 · Cited by 3 · see citing works
Dąbrowska, M., Kępczyńska, A., Goździk, K., Nowak, N., Uram, Ł. S., Skoneczny, M., Doligalska, M., & Sikora, E. (2025) · Histochemistry and Cell Biology · doi:10.1007/s00418-025-02363-8 · Cited by 3 · see citing works
Advancing Alzheimer's disease treatment: A literature review on senolytic intervention
Onuh, V. C. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251376540 · Cited by 2 · see citing works
Liu, J., Lian, H., Zhou, P., & Chen, D. (2021) · E3S Web of Conferences · doi:10.1051/e3sconf/202127103015 · Cited by 2 · see citing works
Genetic and Epigenetic Influences on Cutaneous Cellular Senescence
Sarkar, T. J., Hermsmeier, M., Ross, J. L., & Herron, G. S. (2021) · Physiology · doi:10.5772/intechopen.101152 · Cited by 1 · see citing works
Accelerated senescence of bone marrow erythrocyte precursors in myelodysplastic syndrome
Liu, M., Yang, L., Liu, Y., Niu, H., Zhang, M., Shao, Z., Xing, L., & Wang, H. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2494676 · Cited by 1 · see citing works
Hong, M. J., Kim, S. N., Shin, S. H., Ko, J., Park, S., Kim, S. H., Nam, G. B., Park, W. S., Park, B. C., & Kim, H.-J. (2025) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-025-00210-0 · Cited by 1 · see citing works
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Quercetin Mitigates Oxidative Stress-Induced Premature Senescence in SH-SY5Y Neuronal-like Cells
Salamone, F. L., Molonia, M. S., Trischitta, S., Saija, A., Cimino, F., & Speciale, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27135759 · Cited by 2 · see citing works
From cellular senescence towards age-related macular degeneration: the role of telomeres
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Senolytic Therapy as a Preventive Strategy for Low Back PainPreprint
Darband, S. G., Cherif, H., Mannarino, M., Sagir, J., Millecamps, M., Ouellet, J. A., Stone, L. S., & Haglund, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.08.681005
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Ramos, G. S. M. (2026) · Esprint Investigación · doi:10.61347/ei.v5i1.263
Senolytic Therapy as a Preventive Strategy for Spine Degeneration and Pain
Darband, S. G., Cherif, H., Mannarino, M., Sagir, J., Millecamps, M., Ouellet, J. A., Stone, L. S., & Haglund, L. (2026) · Advanced Science · doi:10.1002/advs.202522770
- Authors
- Prieto, L. I., Graves, S. I., & Baker, D. J.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Baker, Darren J.
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2020-04-13
- Volume
- 9
- Issue
- 4
- Pages
- 954
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC7226957
- OpenAlex
- W3015776120
- Cited by
- 41
- References
- 71
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 5
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG53229)
- Cure Alzheimer's Fund (Baker)
- Glenn Foundation for Medical Research (Baker)
- Ellison Medical Foundation (Baker)
- Topics
- Health Sciences › Medicine › Physiology › 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
- cellular senescence, cell cycle arrest, senescence-associated secretory phenotype, senolytics, aging, age-related diseases, healthspan, tumor suppression, wound healing, tissue senescence
- MeSH terms
- Aging, Animals, Mice, Transgenic, Cellular Senescence, Mice
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