Evidence map›Paper›PMID 41513056›Full record

ArticleHeart rhythm2026

Senolytic reduction of senescent cells mitigates atrial arrhythmia vulnerability in aging rabbits.

Elif Sengun, Lily Zhou, Maxfield Kelsey, Nilufer N Turan, Yichun Lu, Anatoli Y Kabakov, Peter Bronk, Eric Mi, Tae Yun Kim, Shilpa Vijayakumar and 14 more

Abstract read
In one paragraph

Article in Heart rhythm, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

24 authors.

Elif SengunThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island; Department of Pharmacology, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Türkiye.
Lily ZhouThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Maxfield KelseyDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island.
Nilufer N TuranThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island; School of Nursing and Health Sciences, Providence College, Providence, Rhode Island.
Yichun LuCardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Anatoli Y KabakovThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Peter BronkThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Eric MiThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Tae Yun KimThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Shilpa VijayakumarThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Dana PriceThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Sade Solola NussbaumThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Christopher SongThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Jun FengThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Frank W SellkeThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Patrycja Dubielecka-SzczerbaThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Department of Hematology & Oncology, Rhode Island Hospital, Providence, Rhode Island.
Federica Del MonteMedical University of South Carolina, Charleston, South Carolina.
Jeanne NerbonneDepartment of Developmental Biology, Medical School of Washington University, St. Louis, Missouri.
B Sonmez Uydes-DoganDepartment of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye, and.
Karim RoderThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
Bum-Rak ChoiThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.
David R Van WagonerDepartment of Heart, Blood and Kidney Research, Cleveland Clinic, Cleveland, Ohio.
John M SedivyDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island.
Gideon KorenThe Warren Alpert Medical School of Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island. Electronic address: gideon_koren@brown.edu.

Funding

Project 3 Genes to Omics-Informed Drugs: Drug Repositioning and Testing to Prevent AF ProgressionsP01HL158502 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Robert Alden Koeth · 2022 to 2026
$16.9M
MECHANISMS OF REPLICATIVE SENESCENCE IN CELLSR01AG016694 · NIA · BROWN UNIVERSITY · PI SEDIVY, JOHN M · 1999 to 2024
$5.7M
NHLBI NIH HHS P01 HL158502NIA NIH HHS R01 AG016694
6 · The paper itself

Abstract

backgroundAtrial fibrillation (AF) is the most common arrhythmia among the elderly and a major contributor to morbidity and mortality. Inflammation plays a central role in AF pathogenesis, and aging is a key independent risk factor. Cellular senescence is a hallmark of aging and contributes to age-related disease through the senescence-associated secretory phenotype (SASP), characterized by proinflammatory and profibrotic factors.

objectiveThis study aimed to determine whether senescent atrial cells contribute to age-related AF risk and whether senolytic therapy can mitigate this phenotype.

methodsYoung (≤1 year) and aged (≥4 years) New Zealand White rabbits were evaluated using optical mapping, patch-clamp electrophysiology, and histologic and molecular analyses. Senescence markers were assessed using senescence-associated β-galactosidase staining, immunofluorescence, and RNA sequencing. Human atrial specimens from patients with and without AF were examined to assess translational relevance. Aged rabbits received the senolytic compound fisetin to evaluate its effects on atrial senescence and arrhythmia susceptibility.

resultsAged rabbits displayed electrophysiological heterogeneity, prolonged action potentials, and increased AF inducibility, recapitulating clinical features of elderly human atria. Atrial tissue from aged rabbits and patients with AF showed an increase in senescent myocytes and myofibroblasts with upregulation of inflammatory SASP genes. SASP factor expression correlated with left atrial diameter in human samples, an AF risk factor. Short-term fisetin treatment eliminated most senescent atrial cells, reduced inducible AF, and decreased reentry activity without impairing atrial function.

conclusionSenescent atrial cells promote a proinflammatory, proarrhythmic substrate predisposing to AF. Senolytic therapy with fisetin alleviates this phenotype, suggesting a potential strategy to prevent age-related AF.

Indexed as

Atrial FibrillationSenescence-Associated Secretory PhenotypeSenotherapeuticsAction PotentialsAgedAgingAnimalsDisease Models, AnimalElectrocardiographyFemaleFlavonolsHeart AtriaHumansMaleMiddle AgedPatch-Clamp TechniquesfisetinFlavonolsSenotherapeuticsAgingAtrial fibrillationAtrial remodelingCellular senescenceInflammationSenescence-associated secretory phenotype (SASP)Senolytic therapy

Identifiers

PMID41513056
PMCPMC13075518

What Socratic holds

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LicenceCC BY
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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 Socratic graph.