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High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP

Autophagy defects accelerate aging, while stimulation of autophagy decelerates aging. Acyl‐coenzyme A binding protein (ACBP), which is encoded by a diazepam‐binding inhibitor (DBI), acts as an extracellular feedback regulator of autophagy. As shown here, knockout of the gene coding for the yeast ort...

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Autores principales: Montégut, Léa, Joseph, Adrien, Chen, Hui, Abdellatif, Mahmoud, Ruckenstuhl, Christoph, Motiño, Omar, Lambertucci, Flavia, Anagnostopoulos, Gerasimos, Lachkar, Sylvie, Dichtinger, Silvia, Maiuri, Maria Chiara, Goldwasser, François, Blanchet, Benoit, Fumeron, Frédéric, Martins, Isabelle, Madeo, Frank, Kroemer, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835587/
https://www.ncbi.nlm.nih.gov/pubmed/36510662
http://dx.doi.org/10.1111/acel.13751
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author Montégut, Léa
Joseph, Adrien
Chen, Hui
Abdellatif, Mahmoud
Ruckenstuhl, Christoph
Motiño, Omar
Lambertucci, Flavia
Anagnostopoulos, Gerasimos
Lachkar, Sylvie
Dichtinger, Silvia
Maiuri, Maria Chiara
Goldwasser, François
Blanchet, Benoit
Fumeron, Frédéric
Martins, Isabelle
Madeo, Frank
Kroemer, Guido
author_facet Montégut, Léa
Joseph, Adrien
Chen, Hui
Abdellatif, Mahmoud
Ruckenstuhl, Christoph
Motiño, Omar
Lambertucci, Flavia
Anagnostopoulos, Gerasimos
Lachkar, Sylvie
Dichtinger, Silvia
Maiuri, Maria Chiara
Goldwasser, François
Blanchet, Benoit
Fumeron, Frédéric
Martins, Isabelle
Madeo, Frank
Kroemer, Guido
author_sort Montégut, Léa
collection PubMed
description Autophagy defects accelerate aging, while stimulation of autophagy decelerates aging. Acyl‐coenzyme A binding protein (ACBP), which is encoded by a diazepam‐binding inhibitor (DBI), acts as an extracellular feedback regulator of autophagy. As shown here, knockout of the gene coding for the yeast orthologue of ACBP/DBI (ACB1) improves chronological aging, and this effect is reversed by knockout of essential autophagy genes (ATG5, ATG7) but less so by knockout of an essential mitophagy gene (ATG32). In humans, ACBP/DBI levels independently correlate with body mass index (BMI) as well as with chronological age. In still‐healthy individuals, we find that high ACBP/DBI levels correlate with future cardiovascular events (such as heart surgery, myocardial infarction, and stroke), an association that is independent of BMI and chronological age, suggesting that ACBP/DBI is indeed a biomarker of “biological” aging. Concurringly, ACBP/DBI plasma concentrations correlate with established cardiovascular risk factors (fasting glucose levels, systolic blood pressure, total free cholesterol, triglycerides), but are inversely correlated with atheroprotective high‐density lipoprotein (HDL). In mice, neutralization of ACBP/DBI through a monoclonal antibody attenuates anthracycline‐induced cardiotoxicity, which is a model of accelerated heart aging. In conclusion, plasma elevation of ACBP/DBI constitutes a novel biomarker of chronological aging and facets of biological aging with a prognostic value in cardiovascular disease.
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spelling pubmed-98355872023-01-18 High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP Montégut, Léa Joseph, Adrien Chen, Hui Abdellatif, Mahmoud Ruckenstuhl, Christoph Motiño, Omar Lambertucci, Flavia Anagnostopoulos, Gerasimos Lachkar, Sylvie Dichtinger, Silvia Maiuri, Maria Chiara Goldwasser, François Blanchet, Benoit Fumeron, Frédéric Martins, Isabelle Madeo, Frank Kroemer, Guido Aging Cell Short Communications Autophagy defects accelerate aging, while stimulation of autophagy decelerates aging. Acyl‐coenzyme A binding protein (ACBP), which is encoded by a diazepam‐binding inhibitor (DBI), acts as an extracellular feedback regulator of autophagy. As shown here, knockout of the gene coding for the yeast orthologue of ACBP/DBI (ACB1) improves chronological aging, and this effect is reversed by knockout of essential autophagy genes (ATG5, ATG7) but less so by knockout of an essential mitophagy gene (ATG32). In humans, ACBP/DBI levels independently correlate with body mass index (BMI) as well as with chronological age. In still‐healthy individuals, we find that high ACBP/DBI levels correlate with future cardiovascular events (such as heart surgery, myocardial infarction, and stroke), an association that is independent of BMI and chronological age, suggesting that ACBP/DBI is indeed a biomarker of “biological” aging. Concurringly, ACBP/DBI plasma concentrations correlate with established cardiovascular risk factors (fasting glucose levels, systolic blood pressure, total free cholesterol, triglycerides), but are inversely correlated with atheroprotective high‐density lipoprotein (HDL). In mice, neutralization of ACBP/DBI through a monoclonal antibody attenuates anthracycline‐induced cardiotoxicity, which is a model of accelerated heart aging. In conclusion, plasma elevation of ACBP/DBI constitutes a novel biomarker of chronological aging and facets of biological aging with a prognostic value in cardiovascular disease. John Wiley and Sons Inc. 2022-12-12 /pmc/articles/PMC9835587/ /pubmed/36510662 http://dx.doi.org/10.1111/acel.13751 Text en © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communications
Montégut, Léa
Joseph, Adrien
Chen, Hui
Abdellatif, Mahmoud
Ruckenstuhl, Christoph
Motiño, Omar
Lambertucci, Flavia
Anagnostopoulos, Gerasimos
Lachkar, Sylvie
Dichtinger, Silvia
Maiuri, Maria Chiara
Goldwasser, François
Blanchet, Benoit
Fumeron, Frédéric
Martins, Isabelle
Madeo, Frank
Kroemer, Guido
High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP
title High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP
title_full High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP
title_fullStr High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP
title_full_unstemmed High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP
title_short High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP
title_sort high plasma concentrations of acyl‐coenzyme a binding protein (acbp) predispose to cardiovascular disease: evidence for a phylogenetically conserved proaging function of acbp
topic Short Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835587/
https://www.ncbi.nlm.nih.gov/pubmed/36510662
http://dx.doi.org/10.1111/acel.13751
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