Evidence map›Paper›PMID 34103349›Full record

ArticleScience (New York, N.Y.)2021

Senolytics reduce coronavirus-related mortality in old mice.

Christina D Camell, Matthew J Yousefzadeh, Yi Zhu, Larissa G P Langhi Prata, Matthew A Huggins, Mark Pierson, Lei Zhang, Ryan D O'Kelly, Tamar Pirtskhalava, Pengcheng Xun and 24 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
211citing papers in PubMed, 3 pooled it
30.3field-weighted citation impact, top 1% of its field
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

211 citing papers in PubMed, 3 syntheses or guidelines pooled it, 312 citations in OpenAlex.

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  17. p21Nature aging · 2026
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151 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 5 institutions in 1 country.

Christina D Camell *Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0001-7847-3543
Matthew J Yousefzadeh *Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0003-2869-1029
Yi Zhu *Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-3876-3156
Larissa G P Langhi Prata *Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-9617-8089
Matthew A HugginsDepartment of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0003-2964-8719
Mark PiersonDepartment of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.
Lei ZhangInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Ryan D O'KellyInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Tamar PirtskhalavaRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Pengcheng XunDepartment of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, IN, USA.ORCID 0000-0002-6245-4505
Keisuke EjimaDepartment of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, IN, USA.ORCID 0000-0002-1185-3987
Ailing XueRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Utkarsh TripathiRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-7101-8430
Jair Machado Espindola-NettoRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Nino GiorgadzeRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Elizabeth J AtkinsonRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-1191-3775
Christina L InmanRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Kurt O JohnsonRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-0682-4687
Stephanie H CholenskyInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Timothy W CarlsonMasonic Cancer Center Comparative Pathology Shared Resource, University of Minnesota, St. Paul, MN, USA.ORCID 0000-0001-9756-4192
Nathan K LeBrasseurRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-2002-0418
Sundeep KhoslaRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-2936-4372
M Gerard O'SullivanMasonic Cancer Center Comparative Pathology Shared Resource, University of Minnesota, St. Paul, MN, USA.ORCID 0000-0002-5463-1153
David B AllisonDepartment of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, IN, USA.ORCID 0000-0003-3566-9399
Stephen C JamesonDepartment of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0001-9137-1146
Alexander MevesDepartment of Dermatology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-7462-8288
Ming LiDepartment of Dermatology, Mayo Clinic, Rochester, MN, USA.
Y S PrakashDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-2968-224X
Sergio E ChiarellaDivision of Allergic Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-0445-4929
Sara E HamiltonDepartment of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA. probbins@umn.edu kirkland.james@mayo.edu lniedern@umn.edu tchkonia.tamar@mayo.edu hamil062@umn.edu.ORCID 0000-0002-3768-7622
Tamara TchkoniaRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA. probbins@umn.edu kirkland.james@mayo.edu lniedern@umn.edu tchkonia.tamar@mayo.edu hamil062@umn.edu.ORCID 0000-0003-4623-7145
Laura J NiedernhoferInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA. probbins@umn.edu kirkland.james@mayo.edu lniedern@umn.edu tchkonia.tamar@mayo.edu hamil062@umn.edu.ORCID 0000-0002-1074-1385
James L KirklandRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA. probbins@umn.edu kirkland.james@mayo.edu lniedern@umn.edu tchkonia.tamar@mayo.edu hamil062@umn.edu.ORCID 0000-0003-1676-4905
Paul D RobbinsInstitute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA. probbins@umn.edu kirkland.james@mayo.edu lniedern@umn.edu tchkonia.tamar@mayo.edu hamil062@umn.edu.ORCID 0000-0003-1068-7099
University of Minnesota · USMayo Clinic in Florida · USMayo Clinic in Arizona · USIndiana University Bloomington · USMayo Clinic · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla · 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 Zhengdong Zhang · 2017 to 2026
$24.5M
Sex hormones and arthritis in a long lived animal modelP30AG050886 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Jianhua Zhang · 2015 to 2026
$11.3M
PROTEOMICSP01AG043376 · NIA · UNIVERSITY OF MINNESOTA · PI ROBBINS, PAUL D. · 2013 to 2019
$11.2M
Effect of Aging on Preadipocyte DifferentiationR37AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 2016 to 2025
$6.6M
Translational Geroscience NetworkR33AG061456 · NIA · MAYO CLINIC ROCHESTER · PI JAMES L. KIRKLAND, STEPHEN B. KRITCHEVSKY · 2019 to 2026
$6.2M
Nathan Shock Centers Coordinating CenterU24AG056053 · NIA · AMERICAN FEDERATION FOR AGING RESEARCH · PI STEVEN N. AUSTAD, Stephanie Lederman · 2017 to 2026
$6.1M
Effect of Aging on Preadipocyte DifferentiationR01AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 1997 to 2012
$3.7M
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
Generation and function of "long-lived effector" memory CD8 T cellsR01AI116678 · NIAID · UNIVERSITY OF MINNESOTA · PI HAMILTON HART, SARA ELIZABETH · 2015 to 2019
$2.3M
Aging and Resiliency in Mice: Optimizing Assessment Protocols and Testing InterventionsR01AG053832 · NIA · MAYO CLINIC ROCHESTER · PI LEBRASSEUR, NATHAN K, MILLER, JORDAN D · 2016 to 2020
$2.0M
NCI NIH HHS K08 CA215105NCI NIH HHS P30 CA077598NIAID NIH HHS R01 AI116678NIA NIH HHS K99 AG058800NIA NIH HHS P01 AG043376NIA NIH HHS P01 AG062413NIA NIH HHS P30 AG050886NIA NIH HHS R00 AG058800NIA NIH HHS R01 AG013925NIA NIH HHS R01 AG053832NIA NIH HHS R01 AG063543NIA NIH HHS R33 AG061456NIA NIH HHS R37 AG013925NIA NIH HHS U19 AG056278NIA NIH HHS U24 AG056053
6 · The paper itself

Abstract

The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression of viral entry proteins and reducing antiviral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse β-coronavirus experienced increased senescence and inflammation, with nearly 100% mortality. Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.

Indexed as

AgingAnimalsCell LineCellular SenescenceCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentDasatinibFemaleFlavonolsGene Expression RegulationHumansLipopolysaccharidesMaleMiceMice, Inbred C57BLDasatinibfisetinFlavonolsLipopolysaccharidesPathogen-Associated Molecular Pattern MoleculesQuercetinReceptors, CoronavirusSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID34103349
PMCPMC8607935
OpenAlexW3172838821

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.