Evidence map›Paper›PMID 35616058›Full record

ArticleCirculation2022

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.

Mahmoud Abdellatif, Viktoria Trummer-Herbst, Alexander Martin Heberle, Alina Humnig, Tobias Pendl, Sylvère Durand, Giulia Cerrato, Sebastian J Hofer, Moydul Islam, Julia Voglhuber and 15 more

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

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
11.2field-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

54 citing papers in PubMed, 98 citations in OpenAlex.

  1. Trial
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  5. Small-molecule IGF1R inhibitors extend healthspan in a mouse model.bioRxiv : the preprint server for biology · 2026
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  19. Obesity accelerates cardiovascular ageing.European heart journal · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 7 institutions in 8 countries.

Mahmoud AbdellatifDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.ORCID 0000-0002-5042-9054
Viktoria Trummer-HerbstDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.
Alexander Martin HeberleInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria (A.M.H., J.M.R.P., K.T.).ORCID 0000-0001-6414-8707
Alina HumnigDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.
Tobias PendlInstitute of Molecular Biosciences, NAWI Graz (T.P., S.J.H., T.E., F.M.), Washington University School of Medicine, Saint Louis, MO.
Sylvère DurandMetabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France (M.A., S.D., G.C., O.K., G.K.).
Giulia CerratoMetabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France (M.A., S.D., G.C., O.K., G.K.).ORCID 0000-0003-2755-2860
Sebastian J HoferBioTechMed Graz, Austria (M.A., S.J.H., J.V., G.H., P.P.R., T.E., F.M., S.S.).ORCID 0000-0002-0756-0014
Moydul IslamUniversity of Graz, Austria. Department of Chemistry (M.I.), Washington University School of Medicine, Saint Louis, MO.ORCID 0000-0002-3828-9562
Julia VoglhuberBioTechMed Graz, Austria (M.A., S.J.H., J.V., G.H., P.P.R., T.E., F.M., S.S.).ORCID 0000-0003-0102-7902
José Miguel Ramos PittolInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria (A.M.H., J.M.R.P., K.T.).ORCID 0000-0003-3753-5394
Oliver KeppMetabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France (M.A., S.D., G.C., O.K., G.K.).ORCID 0000-0002-6081-9558
Gerald HoeflerDiagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Pathology (G.H.), Medical University of Graz, Austria.
Albrecht SchmidtDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.
Peter P RainerDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.ORCID 0000-0002-2840-6454
Daniel ScherrDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.
Dirk von LewinskiDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.
Egbert BispingDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.ORCID 0000-0003-4623-0330
Julie R McMullenBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia (J.R.M.).
Abhinav DiwanCenter for Cardiovascular Research and Cardiovascular Division, Department of Medicine (M.I., A.D.), Washington University School of Medicine, Saint Louis, MO.
Tobias EisenbergBioTechMed Graz, Austria (M.A., S.J.H., J.V., G.H., P.P.R., T.E., F.M., S.S.).ORCID 0000-0003-3559-1130
Frank MadeoBioTechMed Graz, Austria (M.A., S.J.H., J.V., G.H., P.P.R., T.E., F.M., S.S.).
Kathrin ThedieckInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria (A.M.H., J.M.R.P., K.T.).ORCID 0000-0002-9069-2930
Guido KroemerMetabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France (M.A., S.D., G.C., O.K., G.K.).ORCID 0000-0002-9334-4405
Simon SedejDepartment of Cardiology (M.A., V.T.-H., A.H., J.V., A.S., P.P.R., D.S., D.v.L. E.B., S.S.), Medical University of Graz, Austria.ORCID 0000-0002-4419-6821
Medical University of Graz · ATWashington University in St. Louis · USInserm · FRUniversität Innsbruck · ATBaker Heart and Diabetes Institute · AUBioTechMed-Graz · ATCarl von Ossietzky Universität Oldenburg · DE

Funding

ROLE OF AUTOPHAGIC FLUX IN CARDIAC MYOCYTE VIABILITYR01HL107594 · NHLBI · WASHINGTON UNIVERSITY · PI Abhinav Diwan · 2011 to 2026
$5.9M
Maternal obesity and cardiometabolic health in the offspringR01HL143431 · NHLBI · WASHINGTON UNIVERSITY · PI DIWAN, ABHINAV · 2018 to 2021
$2.5M
Austrian Science Fund FWF I 3301Austrian Science Fund FWF P 27637NHLBI NIH HHS R01 HL107594NHLBI NIH HHS R01 HL143431
6 · The paper itself

Abstract

backgroundThe insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

methodsWe performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic flux, and targeted metabolome profiling, and immunoblots of key IGF1R downstream targets in mouse and human explanted failing and nonfailing hearts, as well.

resultsYoung mice with increased IGF1R signaling exhibited superior cardiac function that progressively declined with aging in an accelerated fashion compared with wild-type animals, resulting in heart failure and a reduced lifespan. In contrast, mice with low cardiac IGF1R signaling exhibited inferior cardiac function early in life, but superior cardiac performance during aging, and increased maximum lifespan, as well. Mechanistically, the late-life detrimental effects of IGF1R activation correlated with suppressed autophagic flux and impaired oxidative phosphorylation in the heart. Low IGF1R activity consistently improved myocardial bioenergetics and function of the aging heart in an autophagy-dependent manner. In humans, failing hearts, but not those with compensated hypertrophy, displayed exaggerated IGF1R expression and signaling activity.

conclusionsOur findings indicate that the relationship between IGF1R signaling and cardiac health is not linear, but rather biphasic. Hence, pharmacological inhibitors of the IGF1 pathway, albeit unsuitable for young individuals, might be worth considering in older adults.

Indexed as

Insulin-Like Growth Factor ILongevityAgedAnimalsHealth PromotionHumansMaleMiceMyocytes, CardiacPhosphatidylinositol 3-KinasesReceptor, IGF Type 1Insulin-Like Growth Factor IPhosphatidylinositol 3-KinasesReceptor, IGF Type 1agingautophagycardiomyopathiesinsulin-like growth factor 1mitochondriamousephosphatidylinositol 3-kinases

Identifiers

PMID35616058
PMCPMC9203038
OpenAlexW4282939243

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.