Ovid Technologies (Wolters Kluwer Health)

Circulation

, volume 145 , issue 25 , pages 1853-1866

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

Mahmoud Abdellatif ^{1, 2, 3, 4}

Viktoria Trummer-Herbst ¹

Alexander Martin Heberle ⁵

Alina Humnig ¹

Tobias Pendl ⁶

Sylvère Durand ^{2, 3}

Giulia Cerrato ^{2, 3}

Sebastian J. Hofer ^{4, 6, 7}

Moydul Islam ^{8, 9}

Julia Voglhuber ⁴

José Miguel Ramos Pittol ⁵

Guido Kroemer ^{2, 3}

Gerald Hoefler ^{4, 10}

Albrecht Schmidt ¹

Peter P. Rainer ^{1, 4}

Daniel Scherr ¹

Dirk von Lewinski ¹

Egbert Bisping ¹

Julie R McMullen ¹¹

Abhinav Diwan ^{9, 12}

Tobias Eisenberg ^{4, 6, 7}

Frank Madeo ^{4, 6, 7}

Kathrin Thedieck ^{5, 13, 14}

Guido Kroemer ^{2, 3, 15}

Simon Sedej ^{1, 4, 16}

Hide authors affiliations Show authors affiliations: 16 affiliations

Department 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. |

Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France (M.A., S.D., G.C., O.K., G.K.). |

Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France (M.A., S.D., G.C., O.K., G.K.).

Sorbonne University

Institut Universitaire de France

French Institute of Health and Medical Research

Centre de Recherche des Cordeliers

⁴

BioTechMed Graz, Austria (M.A., S.J.H., J.V., G.H., P.P.R., T.E., F.M., S.S.). |

⁵

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria (A.M.H., J.M.R.P., K.T.). |

⁶

Institute of Molecular Biosciences, NAWI Graz (T.P., S.J.H., T.E., F.M.), Washington University School of Medicine, Saint Louis, MO. |

⁷

Field of Excellence BioHealth (S.J.H., T.E., F.M.), Washington University School of Medicine, Saint Louis, MO. |

⁸

University of Graz, Austria. Department of Chemistry (M.I.), Washington University School of Medicine, Saint Louis, MO. |

⁹

Center for Cardiovascular Research and Cardiovascular Division, Department of Medicine (M.I., A.D.), Washington University School of Medicine, Saint Louis, MO. |

¹⁰

Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Pathology (G.H.), Medical University of Graz, Austria. |

¹¹

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (J.R.M.). |

¹²

John Cochran Veterans Affairs Medical Center, Saint Louis, MO (A.D.).

¹³

Department of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, The Netherlands (K.T.). |

¹⁴

Department for Neuroscience, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Germany (K.T.). |

¹⁵

Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, France (G.K.). |

¹⁶

Institute of Physiology, Faculty of Medicine, University of Maribor, Slovenia (S.S.). |

Publication type: Journal Article

Publication date: 2022-06-21

Ovid Technologies (Wolters Kluwer Health)

Circulation

scimago Q1

wos Q1

SJR: 8.668

CiteScore: 45.1

Impact factor: 38.6

ISSN: 00097322, 15244539

DOI: 10.1161/CIRCULATIONAHA.122.059863

Copy DOI

PubMed ID: 35616058

Cardiology and Cardiovascular Medicine

Physiology (medical)

Abstract

Background:

The 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.

Methods:

We 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.

Results:

Young 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.

Conclusions:

Our 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.

Found

1 citation

Moskalev Alexey

205 publications, 7 262 citations, 16 reviews

h-index: 42

Petrovsky National Research Centre of Surgery

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GOST Copy

Abdellatif M. et al. Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity // Circulation. 2022. Vol. 145. No. 25. pp. 1853-1866.

GOST all authors (up to 50) Copy

Abdellatif M., Trummer-Herbst V., Heberle A. M., Humnig A., Pendl T., Durand S., Cerrato G., Hofer S. J., Islam M., Voglhuber J., Ramos Pittol J. M., Kroemer G., Hoefler G., Schmidt A., Rainer P. P., Scherr D., von Lewinski D., Bisping E., McMullen J. R., Diwan A., Eisenberg T., Madeo F., Thedieck K., Kroemer G., Sedej S. Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity // Circulation. 2022. Vol. 145. No. 25. pp. 1853-1866.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1161/CIRCULATIONAHA.122.059863

UR - https://doi.org/10.1161/CIRCULATIONAHA.122.059863

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

T2 - Circulation

AU - Abdellatif, Mahmoud

AU - Trummer-Herbst, Viktoria

AU - Heberle, Alexander Martin

AU - Humnig, Alina

AU - Pendl, Tobias

AU - Durand, Sylvère

AU - Cerrato, Giulia

AU - Hofer, Sebastian J.

AU - Islam, Moydul

AU - Voglhuber, Julia

AU - Ramos Pittol, José Miguel

AU - Kroemer, Guido

AU - Hoefler, Gerald

AU - Schmidt, Albrecht

AU - Rainer, Peter P.

AU - Scherr, Daniel

AU - von Lewinski, Dirk

AU - Bisping, Egbert

AU - McMullen, Julie R

AU - Diwan, Abhinav

AU - Eisenberg, Tobias

AU - Madeo, Frank

AU - Thedieck, Kathrin

AU - Kroemer, Guido

AU - Sedej, Simon

PY - 2022

DA - 2022/06/21

PB - Ovid Technologies (Wolters Kluwer Health)

SP - 1853-1866

IS - 25

VL - 145

PMID - 35616058

SN - 0009-7322

SN - 1524-4539

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2022_Abdellatif,

author = {Mahmoud Abdellatif and Viktoria Trummer-Herbst and Alexander Martin Heberle and Alina Humnig and Tobias Pendl and Sylvère Durand and Giulia Cerrato and Sebastian J. Hofer and Moydul Islam and Julia Voglhuber and José Miguel Ramos Pittol and Guido Kroemer and Gerald Hoefler and Albrecht Schmidt and Peter P. Rainer and Daniel Scherr and Dirk von Lewinski and Egbert Bisping and Julie R McMullen and Abhinav Diwan and Tobias Eisenberg and Frank Madeo and Kathrin Thedieck and Guido Kroemer and Simon Sedej},

title = {Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity},

journal = {Circulation},

year = {2022},

volume = {145},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

month = {jun},

url = {https://doi.org/10.1161/CIRCULATIONAHA.122.059863},

number = {25},

pages = {1853--1866},

doi = {10.1161/CIRCULATIONAHA.122.059863}

}

MLA

Cite this

MLA Copy

Abdellatif, Mahmoud, et al. “Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.” Circulation, vol. 145, no. 25, Jun. 2022, pp. 1853-1866. https://doi.org/10.1161/CIRCULATIONAHA.122.059863.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Journal

Circulation

scimago Q1

wos Q1

SJR

8.668

CiteScore

45.1

Impact factor

38.6

ISSN

00097322 (Print)

15244539 (Electronic)

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