Tier 3 — preclinical

The Achilles' heel of senescent cells: from transcriptome to senolytic drugs

Yi Zhu, Tamara Tchkonia, Tamar Pirtskhalava, Adam C Gower, Husheng Ding, Nino Giorgadze, Allyson K Palmer, Yuji Ikeno, Gene B Hubbard, Marc Lenburg, Steven P O'Hara, Nicholas F LaRusso, Jordan D Miller, Carolyn M Roos, Grace C Verzosa, Nathan K LeBrasseur, Jonathan D Wren, Joshua N Farr, Sundeep Khosla, Michael B Stout, Sara J McGowan, Heike Fuhrmann-Stroissnigg, Aditi U Gurkar, Jing Zhao, Debora Colangelo, Akaitz Dorronsoro, Yuan Yuan Ling, Amira S Barghouthy, Diana C Navarro, Tokio Sano, Paul D Robbins, Laura J Niedernhofer, James L Kirkland
Aging cell 2015 14(4):644

Bibliography

PubMed
PMID 25754370
PubMed Central
PMC4531078
DOI
10.1111/acel.12344
Funding
Indexed grant support: AG044396 — NIA NIH HHS — United States; R01 DK057993 — NIDDK NIH HHS — United States; AG041122 — NIA NIH HHS — United States; F30 AG046061 — NIA NIH HHS — United States; P30 AG013319 — NIA NIH HHS — United States; AG031736 — NIA NIH HHS — United States; UL1-TR000157 — NCATS NIH HHS — United States; P01 AG041122 — NIA NIH HHS — United States; HL111121 — NHLBI NIH HHS — United States; P30 DK084567 — NIDDK NIH HHS — United States; AG013925 — NIA NIH HHS — United States; R01 HL111121 — NHLBI NIH HHS — United States; DK050456 — NIDDK NIH HHS — United States; AG043376 — NIA NIH HHS — United States; P01 AG043376 — NIA NIH HHS — United States. The indexed list may not contain the complete funding declaration.
Competing interests
A competing-interest declaration was not available in the indexed record or the disclosure metadata used for this entry.

Study snapshot

DesignSenolytic discovery experiments in cells and mouse models
ModelAnimal and laboratory research
SampleHuman-derived cell cultures and multiple mouse models; no treated human cohort
InterventionDasatinib, quercetin, and their combination in cell-type-specific assays and mouse interventions
DurationExperiment-dependent acute and intermittent schedules
EndpointsSenescence-related measurements

What the study showed, in plain terms

Published in 2015, this source examined senescence and longevity. Design: Senolytic discovery experiments in cells and mouse models. Sample/model: Human-derived cell cultures and multiple mouse models; no treated human cohort. The exposure or intervention was Dasatinib, quercetin, and their combination in cell-type-specific assays and mouse interventions. Follow-up or treatment period: Experiment-dependent acute and intermittent schedules.

Quercetin and dasatinib had different cell-type effects; the combination reduced selected senescence markers and improved some mouse functional outcomes.

Human-derived cells are not a human clinical trial. The study does not establish that oral quercetin alone clears senescent cells or extends life in people.

Continue with Quercetin Data Center

For topic-level interpretation, read Is Quercetin a Senolytic? Human Evidence vs Longevity Claims. This is a related guide; the citation panel separately identifies articles that directly cite this paper.

Key findings

  • Quercetin and dasatinib had different cell-type effects; the combination reduced selected senescence markers and improved some mouse functional outcomes.
  • The recorded outcome domains were Senescence-related measurements.
  • The result applies to the tested exposure: Dasatinib, quercetin, and their combination in cell-type-specific assays and mouse interventions; Experiment-dependent acute and intermittent schedules.

What this study can and cannot tell us

  • Human-derived cells are not a human clinical trial. The study does not establish that oral quercetin alone clears senescent cells or extends life in people.
  • Cell concentrations, species, disease models and experimental routes cannot be converted directly into an effective or safe oral human regimen.
  • Source basis: Source check: PubMed abstract and indexed metadata; full methods were not independently confirmed for this entry. Missing method details, funding information or participant denominators are not inferred.

Related papers in the corpus

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Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design
Alistaire D Ruggiero et al. · GeroScience · 2023
Tier 3
Senolytics improve physical function and increase lifespan in old age
Ming Xu et al. · Nature medicine · 2018

Citation network

Articles citing this research paper

2 articles

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology