Evidence map›Paper›PMID 40306856›Full record

ArticleJACC. Basic to translational science2025

Proteostatic Imbalance Drives the Pathogenesis and Age-Related Exacerbation of Heart Failure With Preserved Ejection Fraction.

Kamil A Kobak, Weronika Zarzycka, Catherine J King, Agnieszka K Borowik, Frederick F Peelor, Leslie M Baehr, Mario Leutert, Ricard A Rodriguez-Mias, Judit Villén, Sue C Bodine and 3 more

Abstract read
In one paragraph

Article in JACC. Basic to translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
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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.

Kamil A KobakAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Weronika ZarzyckaAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Catherine J KingAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Agnieszka K BorowikAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Frederick F PeelorAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Leslie M BaehrAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Mario LeutertDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Ricard A Rodriguez-MiasDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Judit VillénDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Sue C BodineAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
Michael T KinterAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Benjamin F MillerAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
Ying Ann ChiaoAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address: ann-chiao@omrf.org.

Funding

University of Washington Nathan Shock Center of Excellence in the Basic Biology of AgingP30AG013280 · NIA · UNIVERSITY OF WASHINGTON · PI David J. Marcinek, Jessica E Young · 1995 to 2026
$27.1M
Emergent properties of signaling network degradation that mediate homeostatic failure during agingR01AG056359 · NIA · UNIVERSITY OF WASHINGTON · PI KAEBERLEIN, MATT, VILLEN, JUDIT · 2017 to 2021
$2.9M
NIA NIH HHS P30 AG013280NIA NIH HHS R01 AG056359
6 · The paper itself

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of hospitalization and mortality in older adults, yet the role of aging in its pathogenesis remains unclear. Old male mice subjected to chronic metabolic and hypertensive stress (2-hit) developed a more severe HFpEF phenotype compared with young counterparts. We identified that age-related disruptions in protein quality control (PQC) worsens proteostatic stress in HFpEF. Mammalian target of rapamycin complex 1 (mTORC1), a key regulator of PQC, is activated by both aging and 2-hit stress, and cardiac-specific mTORC1 inhibition protects against HFpEF. Our findings highlight the need to integrate aging into preclinical models of HFpEF and suggest targeting PQC as a therapeutic strategy.

Indexed as

autophagycardiac agingHFpEFmTORC1protein degradationprotein quality controlprotein synthesisproteostasis

Identifiers

PMID40306856
PMCPMC12134603

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.