Evidence map›Paper›PMID 42734482›Full record

ArticleExperimental physiology2026

Clearance of p16-positive cardiac cells improves age-related cardiac remodeling in mice.

Mozhdeh Mehdizadeh, Martin Mackasey, Kimia Gharagozloo, Martin Aguilar, Patrice Naud, Allan Ochs, Nhung Vuong-Robillard, Eric Thorin, Gerardo Ferbeyre, Jean-Claude Tardif and 3 more

Abstract read
In one paragraph

Article in Experimental physiology, 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

13 authors.

Mozhdeh MehdizadehResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Martin MackaseyResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Kimia GharagozlooResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Martin AguilarResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Patrice NaudResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Allan OchsResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.ORCID https://orcid.org/0009-0005-7300-8649
Nhung Vuong-RobillardDepartment of Biochemistry, Université de Montréal and CRCHUM, Montreal, Canada.
Eric ThorinDepartment of Surgery, Université de Montréal, Montreal, Canada.
Gerardo FerbeyreDepartment of Biochemistry, Université de Montréal and CRCHUM, Montreal, Canada.
Jean-Claude TardifResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Martin G SiroisResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Jean Francois TanguayResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
Stanley NattelResearch Center, Montreal Heart Institute, Université de Montréal, Montreal, Canada.ORCID https://orcid.org/0000-0002-5565-3311

Funding

CIHR 478053Fonds de Recherche du Quebec- SantéHeart and Stroke Foundation of Canada 23-0035141
6 · The paper itself

Abstract

Senescent cells are characterized by expression of markers like p16 and secretion of profibrotic and proinflammatory factors. The role of cellular senescence in age-related cardiac remodeling and dysfunction is incompletely understood. This study aimed to: (i) evaluate the effect of p16- positive cell clearance on cardiac function and structure in aging mice, and (ii) assess the role of different cardiac cell-types in the response. Hypertrophy markers, ion channels and calcium handling protein gene expression. Statistical analysis for all panels: one-way ANOVA followed by Tukey's test, significance level P<0.05 (N=6 for each group). Each point represents results from one mouse; bars and horizontal lines are means and SD. NK-ATTAC mice, permitting targeted clearance of p16-positive cells upon exposure to the dimerizing agent AP20187 (AP), were treated with AP or vehicle from 12 to 18 months of age. Cardiac function and structure were assessed with echocardiography, hemodynamics with a Millar catheter. p16-positive cells in various cardiac cell populations were analyzed with Fluorescence-Activated Cell Sorting (FACS) and immunofluorescence imaging. Echocardiography revealed significant attenuation of aging-associated increases in left ventricular mass to diameter at end-diastole (LVDd) and anterior wall thickness at end diastole (LVAWTd) in Aged-AP mice versus Aged-Vehicle. Diastolic dysfunction in vehicle mice normalized with AP treatment. FACS results indicated clearance of p16-positive fibroblasts with AP. Immunofluorescence imaging indicated reduced p16-positive fibroblasts and cardiomyocytes with AP, implicating them in the effects of p16-positive cell clearance on age-related cardiac remodeling. Exposure of cardiomyocytes to senescent fibroblast products led to upregulation of hypertrophy markers, pointing to paracrine effects on cardiomyocytes. This study highlights the potential contribution of senescent fibroblasts and cardiomyocytes to age-related cardiac remodeling. Modulating senescence might provide a new approach to age-related cardiac diseases like heart failure.

Indexed as

cardiac fibrosiscellular senescencediastolic dysfunction

Identifiers

PMID42734482
PMCPMC13573716

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.