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Cited by 631Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

Cellular senescence: a key therapeutic target in aging and diseases

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Zhang, Lei, Pitcher, Louise E., Yousefzadeh, Matthew J., Niedernhofer, Laura J., Robbins, Paul D., Zhu, Yi·2022·Journal of Clinical Investigation
DOI 10.1172/jci158450PMC PMC9337830
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Abstract

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop a characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary senescence and disrupts tissue homeostasis, resulting in loss of tissue repair and regeneration. The use of transgenic mouse models in which SnCs can be genetically ablated has established a key role for SnCs in driving aging and age-related disease. Importantly, senotherapeutics have been developed to pharmacologically eliminate SnCs, termed senolytics, or suppress the SASP and other markers of senescence, termed senomorphics. Based on extensive preclinical studies as well as small clinical trials demonstrating the benefits of senotherapeutics, multiple clinical trials are under way. This Review discusses the role of SnCs in aging and age-related diseases, strategies to target SnCs, approaches to discover and develop senotherapeutics, and preclinical and clinical advances of senolytics.

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  • Subtype-specific contributions of primary and secondary senescence to kidney disease and aging remain limited.

    “While the influence of SnCs on surrounding cells is well documented (Gasek et al. 2021; Van Deursen 2014), subtype‐specific contributions of primary and secondary senescence to kidney disease and aging remain limited (Zhang et al. 2022).”

    From Transcriptional Profiling at Single-Cell Resolution Reveals Diversity and Regulatory Networks of Primary and Secondary Senescent Cells (2026) · cites this paper as Zhang et al. 2022

    The sections “Senescent cells in aging and age-related diseases” and “Challenges and future perspectives” describe senescent-cell heterogeneity, secondary senescence, and difficulty distinguishing cell types in disease contexts; the former also lists renal disease among conditions associated with senescent cells. They do not specifically say that knowledge of the respective contributions of primary and secondary senescence to kidney disease and aging is limited. No page numbers were provided in our copy. (LLM, conf=0.76)

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Sorted by citations

Authors
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y.
Affiliations
  • University of Minnesota (US)
  • Mayo Clinic (US)
Corresponding author
  • Robbins, Paul D.
  • Zhu, Yi
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2022-08-01
Volume
132
Issue
15
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
DOI
10.1172/jci158450
PMC
PMC9337830
OpenAlex
W4289028880
Cited by
631
References
64
Citations by year
2026: 165 · 2025: 212 · 2024: 161 · 2023: 85 · 2022: 7 · 2013: 1
FWCI
15.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Investigation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Institutes of Health (ASAP-000592, AG043376, AG056278, AG062413, AG063543)
  • National Institute on Aging (P01AG043376, T32AG029796, U19AG056278, U54AG076041, P01AG062413, R01AG063543)
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, senescent cells, aging, age-related diseases, senescence-associated secretory phenotype, senolytics, senomorphics, senotherapeutics, cell cycle exit, tissue homeostasis, tissue regeneration
MeSH terms
Aging, Animals, Cell Cycle, Mice, Transgenic, Wound Healing, Cellular Senescence, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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