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Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
Open accessAbstract
Aging is a major risk factor for numerous human pathologies, including cardiovascular, metabolic, musculoskeletal, and neurodegenerative conditions and various malignancies. While our understanding of aging is far from complete, recent advances suggest that targeting fundamental aging processes can delay, prevent, or alleviate age-related disorders. Cellular senescence is physiologically beneficial in several contexts, but it has causal roles in multiple chronic diseases. New studies have illustrated the promising feasibility and safety to selectively ablate senescent cells from tissues, a therapeutic modality that holds potential for treating multiple chronic pathologies and extending human healthspan. Here, we review molecular links between cellular senescence and age-associated complications and highlight novel therapeutic avenues that may be exploited to target senescent cells in future geriatric medicine.
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“The target specificity and toxicity to non-senescent cells is still a big hurdle for clinical applications of the current senolyitc treatments.14,15”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [14]
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Cites
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Items 101–195 of 195
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“For instance, treatment with the senomorphic agent rapamycin, which remarkablyalleviatesage-associateddysfunctionsinmodelorganisms, largely resembling the senolytic drug navitoclax, frequently induces hyperlipidaemia, metabolic dysregulation, thrombocytopenia and impairs wound healing 46 .”
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Razali, N., Moriyama, Y., Chiu, Y., Suda, K., & Kono, K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.27.497690 · Cited by 1
“Removal of senescent cells ameliorates various age-associated disorders, including cancer, atherosclerosis, and neurodegenerative disorders (2,3).”
BackgroundFunctional foods in clinical trials in aging intervention
Atukeren, P. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90581-7.00003-7
Resolving Geroplasticity to the Balance of Rejuvenins and Geriatrins
TABIBZADEH, S. S. (2022) · Aging and Disease · doi:10.14336/ad.2022.0414
Cellular senescence as a pathogenic factor and potential therapeutic target in osteoporosis
Larrea, L. P., Rodríguez, M. D. B., Naves‐Díaz, M., & Alonso, C. G. (2023) · Revista de Osteoporosis y Metabolismo Mineral · doi:10.20960/revosteoporosmetabminer.00013 · Cited by 1
Unraveling the Multifactorial Etiology and the Potential Strategies to Overcome Sarcopenia
Tumma, T. (2023) · International Journal of Medical Science and Clinical Research Studies · doi:10.47191/ijmscrs/v3-i9-40
Exercise-Induced Changes in Aging Mouse Hippocampus: A Single-Cell Transcriptomic AnalysisPreprint
Huang, X., Li, X., Yu, J. Z., Wei, C., & Zhang, Y. (2024) · Research Square · doi:10.21203/rs.3.rs-4035975/v1
Molecular imaging for senescent cells-targeted therapeutics in aging and age-related diseases
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“This gene has been extensively studied as an age-related factor in multiple contexts, including gastric cancer [26], pancreatic cancer [27], and chronic obstructive pulmonary disease (COPD) [28].”
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Matus, J., Puebla-Huerta, A., Morgado-Cáceres, P., Quezada-Gutiérrez, C., Casanova-Canelo, C., Rosales‐Rojas, R., Lopez-Dominguez, J. A., Marín, I., Niño, S. A., Cruz, P., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-8172868/v1
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“Far from being a passive or dormant state, senescent cells are metabolically active and exhibit distinct morphological features, including an enlarged, fl attened shape with increased cytoplasmic volume and vacuolization (6).”
Myocardial Aging: Cellular Mechanisms and Therapeutic Perspectives
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“Cell senescence can be caused by various stim(cid:2) uli, and it is not always associated with the chrono(cid:2) logical age of the organism; depending on the type of trigger, replicative, oncogene-induced senescence, and stress-induced premature senescence (SIPS) are distinguished [80, 81].”
Nanocatalytic regulation of age-related diseases
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Stage-dependent transcriptomic changes in human dermal fibroblast senescence model
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Terpenoids as Emerging Senotherapeutics: Mechanistic Insights and Therapeutic Potential
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Biomarkers of senescence in cardiovascular diseases
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Rhenium‐Based β‐Galactosidase Probe Allows Senescence Profiling by Mass Cytometry
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Metabolically Active but Dysfunctional: The Impact of Senescent Cells and SASP
Xu, K., Viniak, S., Shah, P. V., Uddin, I. A., Alam, Z., & Khan, M. W. (2026) · Technology in Cancer Research & Treatment · doi:10.1177/15330338261481909
“6 While transient SASP can aid wound healing and tissue remodeling, persistent SASP is a driver of chronic inflammation and age-related pathology, a phenomenon often termed “inflammaging”.”
The Gut Microbiome as a Mechanistic Link Between the Planetary Health Diet and Healthy Aging
Jarecsny, T., Ceglédi, A., Csípő, T., Fazekas‐Pongor, V., Mózes, N., Csík, B., Zábó, V., Lipécz, Á., Nyáry, D., & Fekete, M. (2026) · Nutrients · doi:10.3390/nu18172864
“Although senescence has important physiological roles in tumor suppression, tissue repair, and wound healing, the progressive accumulation of senescent cells contributes to tissue dysfunction and chronic disease [279].”
Li, H., Lu, S., Wang, H., Yu, D., Zhang, Z., Liu, S., Zhong, M., Xiao, H., & Li, K. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1917548
Metadata
- Authors
- Song, S., Lam, E. W.-F., Tchkonia, T., Kirkland, J. L., & Sun, Y.
- Affiliations
- Binzhou Medical University (CN)
- Imperial College London (GB)
- Mayo Clinic (US)
- Corresponding author
- Sun, Yu
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 45
- Issue
- 7
- Pages
- 578-592
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC7649645
- OpenAlex
- W3014969606
- Cited by
- 195
- References
- 137
- Citations by year
- 2026: 23 · 2025: 27 · 2024: 30 · 2023: 30 · 2022: 40 · 2021: 39 · 2020: 6
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (P01 AG062413, R37-AG013925)
- Cancer Research UK (A12011)
- National Key Research and Development Program of China Stem Cell and Translational Research (2016YFC1302400)
- Breast Cancer Now (2012MayPR070, 2012NovPhD016)
- National Institute for Health Research
- Mayo Clinic
- National Key Research and Development Program of China
- Noaber Foundation
- U.S. Department of Defense (PC111703)
- National Natural Science Foundation of China (31871380, 81472709, 31671425)
- 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, aging, age-related diseases, senolytics, senolytic therapy, healthspan extension, chronic disease, geriatrics, neurodegeneration, cardiovascular disease, cancer
- MeSH terms
- Humans, Neoplasms, Phenotype, Cellular Senescence, Neurodegenerative Diseases
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