The DOI matches its Crossref record; 285 of the 285 references it cites were found in a registry or an index.
Cellular senescence: the good, the bad and the unknown
Open accessAbstract
Cellular senescence is a ubiquitous process with roles in tissue remodelling, including wound repair and embryogenesis. However, prolonged senescence can be maladaptive, leading to cancer development and age-related diseases. Cellular senescence involves cell-cycle arrest and the release of inflammatory cytokines with autocrine, paracrine and endocrine activities. Senescent cells also exhibit morphological alterations, including flattened cell bodies, vacuolization and granularity in the cytoplasm and abnormal organelles. Several biomarkers of cellular senescence have been identified, including SA-βgal, p16 and p21; however, few markers have high sensitivity and specificity. In addition to driving ageing, senescence of immune and parenchymal cells contributes to the development of a variety of diseases and metabolic disorders. In the kidney, senescence might have beneficial roles during development and recovery from injury, but can also contribute to the progression of acute kidney injury and chronic kidney disease. Therapies that target senescence, including senolytic and senomorphic drugs, stem cell therapies and other interventions, have been shown to extend lifespan and reduce tissue injury in various animal models. Early clinical trials confirm that senotherapeutic approaches could be beneficial in human disease. However, larger clinical trials are needed to translate these approaches to patient care.
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“TNF-α is a prominent immune and inflammatory regulator involved in cellular senescence.55,56”
From A pilot study of senolytics to improve cognition and mobility in older adults at risk for Alzheimer's disease (2025) · cites this paper as [55]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Senescence is triggered by stressors such as telomere shortening, DNA damage, oxidative stress, and oncogenic signals5,6,7,8”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [5]
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In the citing paper
“senescent cells accumulate in aged tissues,31,32,33 including the brain.34,35,36”
From Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex (2026) · cites this paper as [33]
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Citations
Cites
3 retracted
- Retracted
- Retracted
Xiong, J., Jiang, P., Zhong, L., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.646511 · Cited by 11
RetractedThe 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
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
Bartkova, J., Hořejší, Z., Koed, K., Krämer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., et al. (2005) · Nature · doi:10.1038/nature03482 · Cited by 2,688
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
Self-citationCellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819
Research works printed but not linked: 1
- Lei, J., Jiang, X., Li, W. & Ren, J. Exosomes from antler stem cells alleviate mesenchymal stem cell senescence and osteoarthritis. Protein Cell 13, 220–226 (2022). · DOI
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Sorted by citations
Cell senescence in liver diseases: pathological mechanism and theranostic opportunity
Sanfeliu-Redondo, D., Gibert-Ramos, A., & Gracia-Sancho, J. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00913-4 · Cited by 117
Millar, C. L., Iloputaife, I., Baldyga, K., Norling, A. M., Boulougoura, A., Vichos, T., Tchkonia, T., Deisinger, A., Pirtskhalava, T., Kirkland, J. L., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105612 · Cited by 88
“55,56 However, it is unclear whether this magnitude of change in TNF-α seen in the STAMINA participants is of biological relevance.”
Self-citationRoadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59
Self-citationWang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28
Dungan, C. M., Wells, J. M., & Murach, K. A. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00553.2022 · Cited by 21
Metadata
- Authors
- Huang, W., Hickson, L. J., Eirin, A., Kirkland, J. L., & Lerman, L. O.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lerman, Lilach O.
- Venue
- Nature Reviews Nephrology
- Published
- 2022-08-03
- Volume
- 18
- Issue
- 10
- Pages
- 611-627
- ISSN
- 1745-8323 (ISSN-L)
- 1759-5061
- 1759-507X
- PMC
- PMC9362342
- OpenAlex
- W4289545008
- Cited by
- 1,150
- References
- 285
- Citations by year
- 2026: 251 · 2025: 399 · 2024: 333 · 2023: 157 · 2022: 10
- FWCI
- 31.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Noaber Foundation
- National Institutes of Health (AG013925)
- National Institute on Aging (R21AG062104, R01AG013925, R33AG061456, R37AG013925)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120292, R01DK122734)
- 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
- cellular senescence, senescence-associated secretory phenotype, senolytics, senotherapeutics, kidney injury, chronic kidney disease, acute kidney injury, tumor suppression, age-related diseases, senescence biomarkers, p16, p21, SA-β-galactosidase, stem cell therapy, tissue remodeling, wound healing, embryonic development
- MeSH terms
- Senotherapeutics, Aging, Animals, Humans, Biomarkers, Cytokines, Cellular Senescence
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