Evidence map›Paper›PMID 42836501›Full record

ArticleAging cell2026

Novel Flavonoid Senotherapeutics Identified by Phenotypic Drug Discovery Reduce Senescence and Improve Multiple Markers of Healthspan.

Lei Justan Zhang, Rahagir Salekeen, Carolina Soto-Palma, Qiuming Wu, Yuanjun He, Osama Elsallabi, Bilel Bdiri, Brian Hughes, Allancer Nunes, Wandi Xu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Lei Justan ZhangMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0001-7409-6090
Rahagir SalekeenMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0001-7045-9106
Carolina Soto-PalmaMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0009-0007-1437-9081
Qiuming WuMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Yuanjun HeThe Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA.
Osama ElsallabiMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0002-8467-5480
Bilel BdiriThe Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA.
Brian HughesMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Allancer NunesMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0003-4158-683X
Wandi XuMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0009-0009-4984-0004
Borui ZhangMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Abdalla MohamedMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Sara J McGowanMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0009-0004-5648-0848
Luise AngeliniMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Ryan O'KellyMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Theodore M KameneckaThe Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA.
Laura J NiedernhoferMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0002-1074-1385
Paul D RobbinsMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0003-1068-7099

Funding

Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla, Nathan K LeBrasseur · 2019 to 2026
$28.7M
Validation and characterization of the identified variants associated with human longevity in mouse modelsU19AG056278 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI JAN VIJG · 2017 to 2026
$24.5M
Midwest Murine-Tissue Mapping Center (MM-TMC)U54AG079754 · NIA · UNIVERSITY OF MINNESOTA · PI GR Scott Budinger, Sundeep Khosla · 2022 to 2026
$11.5M
PROTEOMICSP01AG043376 · NIA · UNIVERSITY OF MINNESOTA · PI ROBBINS, PAUL D. · 2013 to 2019
$11.2M
Minnesota Tissue Mapping Center for Senescent CellsU54AG076041 · NIA · UNIVERSITY OF MINNESOTA · PI Constantin F. Aliferis, LAURA Jane NIEDERNHOFER · 2021 to 2026
$10.5M
Using the senolytic fisetin to suppress mortality in aged mice acutely exposed to murine beta-coronavirusR01AG063543 · NIA · UNIVERSITY OF MINNESOTA · PI NIEDERNHOFER, LAURA JANE · 2019 to 2023
$3.4M
Inflammation, Lipid Metabolism and SenescenceR01AG069819 · NIA · UNIVERSITY OF MINNESOTA · PI CAMELL, CHRISTINA · 2020 to 2024
$1.9M
Glenn Foundation for Medical ResearchNIA NIH HHS P01 AG043376NIA NIH HHS P01 AG062413NIA NIH HHS R01 AG063543NIA NIH HHS R01 AG069819NIA NIH HHS U19 AG056278NIA NIH HHS U54 AG076041NIA NIH HHS U54 AG079754NIH HHS P01 AG043376NIH HHS P01 AG062413NIH HHS R01 AG063543NIH HHS R01 AG069819NIH HHS U19 AG056278NIH HHS U54 AG076041NIH HHS U54 AG079754
6 · The paper itself

Abstract

Senescent cells are a key driver of aging and contribute to many age-related diseases. Senolytics, agents that selectively eliminate senescent cells, offer a promising therapeutic strategy to treat age-related diseases but face significant barriers to clinical translation. Fisetin, a natural flavonoid senolytic, has progressed to clinical trials but is limited by suboptimal efficacy and poor bioavailability. To address these challenges, we developed two novel fisetin-derived flavonoid senolytics, SR29384 and SR31133, using an integrative phenotypic drug discovery approach. These compounds exhibit enhanced senolytic activity, targeting a broad range of senescent cell types, reducing tissue senescence, and improving healthspan-associated parameters in mouse models of aging. Mechanistic investigations combining transcriptomics, machine learning, network pharmacology, and molecular docking revealed that these novel senolytics may target key molecular pathways, including PARP1, CDK2, and possibly BCL-xL to selectively induce apoptosis in senescent cells. These findings provide novel senolytics with high translational potential for clinical applications in promoting healthy aging and treating age-related diseases.

Indexed as

AgingCellular SenescenceDrug DiscoveryFlavonoidsSenotherapeuticsAnimalsBiomarkersFlavonolsHumansMicePhenotypeBiomarkersfisetinFlavonoidsFlavonolsSenotherapeuticsagingfisetin analogflavonoidhealthspanphenotypic drug discoverysenescencesenolyticsenotherapeuticstructure–activity relationship

Identifiers

PMID42836501
PMCPMC13640056

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.