Immunometabolism in the Aging Heart

Structural, functional, and molecular‐level changes in the aging heart are influenced by a dynamic interplay between immune signaling and cellular metabolism that is referred to as immunometabolism. This review explores the crosstalk between cellular metabolic pathways including glycolysis, oxidativ...

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Main Authors: Kranti A. Mapuskar, Barry London, Zeb R. Zacharias, Jon C.D. Houtman, Bryan G. Allen
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.039216
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author Kranti A. Mapuskar
Barry London
Zeb R. Zacharias
Jon C.D. Houtman
Bryan G. Allen
author_facet Kranti A. Mapuskar
Barry London
Zeb R. Zacharias
Jon C.D. Houtman
Bryan G. Allen
author_sort Kranti A. Mapuskar
collection DOAJ
description Structural, functional, and molecular‐level changes in the aging heart are influenced by a dynamic interplay between immune signaling and cellular metabolism that is referred to as immunometabolism. This review explores the crosstalk between cellular metabolic pathways including glycolysis, oxidative phosphorylation, fatty acid metabolism, and the immune processes that govern cardiac aging. With a rapidly aging population that coincides with increased cardiovascular risk and cancer incidence rates, understanding the immunometabolic underpinnings of cardiac aging provides a foundation for identifying therapeutic targets to mitigate cardiac dysfunction. Aging alters the immune environment of the heart by concomitantly driving the changes in immune cell metabolism, mitochondrial dysfunction, and redox signaling. Shifts in these metabolic pathways exacerbate inflammation and impair tissue repair, creating a vicious cycle that accelerates cardiac functional decline. Treatment with cancer therapy further complicates this landscape, as aging‐associated immunometabolic disruptions augment the susceptibility to cardiotoxicity. The current review highlights therapeutic strategies that target the immunometabolic axis to alleviate cardiac aging pathologies. Interventions include modulating metabolic intermediates, improving mitochondrial function, and leveraging immune signaling pathways to restore cardiac health. Advances in immunometabolism thus hold significant potential for translating preclinical findings into therapies that improve the quality of life for the aging population and underscore the need for approaches that address the immunometabolic mechanisms of cardiac aging, providing a framework for future research.
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series Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
spelling doaj-art-a28c80bdcdbf4dc38e26d7d2428d42f52025-08-20T03:24:47ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-01-0114110.1161/JAHA.124.039216Immunometabolism in the Aging HeartKranti A. Mapuskar0Barry London1Zeb R. Zacharias2Jon C.D. Houtman3Bryan G. Allen4Department of Radiation Oncology University of Iowa Hospitals and Clinic, University of Iowa Healthcare Iowa City IA USAHolden Comprehensive Cancer Center, Carver College of Medicine University of Iowa Hospitals and Clinic, University of Iowa Healthcare Iowa City IA USAHolden Comprehensive Cancer Center, Carver College of Medicine University of Iowa Hospitals and Clinic, University of Iowa Healthcare Iowa City IA USAHolden Comprehensive Cancer Center, Carver College of Medicine University of Iowa Hospitals and Clinic, University of Iowa Healthcare Iowa City IA USADepartment of Radiation Oncology University of Iowa Hospitals and Clinic, University of Iowa Healthcare Iowa City IA USAStructural, functional, and molecular‐level changes in the aging heart are influenced by a dynamic interplay between immune signaling and cellular metabolism that is referred to as immunometabolism. This review explores the crosstalk between cellular metabolic pathways including glycolysis, oxidative phosphorylation, fatty acid metabolism, and the immune processes that govern cardiac aging. With a rapidly aging population that coincides with increased cardiovascular risk and cancer incidence rates, understanding the immunometabolic underpinnings of cardiac aging provides a foundation for identifying therapeutic targets to mitigate cardiac dysfunction. Aging alters the immune environment of the heart by concomitantly driving the changes in immune cell metabolism, mitochondrial dysfunction, and redox signaling. Shifts in these metabolic pathways exacerbate inflammation and impair tissue repair, creating a vicious cycle that accelerates cardiac functional decline. Treatment with cancer therapy further complicates this landscape, as aging‐associated immunometabolic disruptions augment the susceptibility to cardiotoxicity. The current review highlights therapeutic strategies that target the immunometabolic axis to alleviate cardiac aging pathologies. Interventions include modulating metabolic intermediates, improving mitochondrial function, and leveraging immune signaling pathways to restore cardiac health. Advances in immunometabolism thus hold significant potential for translating preclinical findings into therapies that improve the quality of life for the aging population and underscore the need for approaches that address the immunometabolic mechanisms of cardiac aging, providing a framework for future research.https://www.ahajournals.org/doi/10.1161/JAHA.124.039216cardiac agingimmunometabolisminflammagingoxidative phosphorylation
spellingShingle Kranti A. Mapuskar
Barry London
Zeb R. Zacharias
Jon C.D. Houtman
Bryan G. Allen
Immunometabolism in the Aging Heart
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiac aging
immunometabolism
inflammaging
oxidative phosphorylation
title Immunometabolism in the Aging Heart
title_full Immunometabolism in the Aging Heart
title_fullStr Immunometabolism in the Aging Heart
title_full_unstemmed Immunometabolism in the Aging Heart
title_short Immunometabolism in the Aging Heart
title_sort immunometabolism in the aging heart
topic cardiac aging
immunometabolism
inflammaging
oxidative phosphorylation
url https://www.ahajournals.org/doi/10.1161/JAHA.124.039216
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AT bryangallen immunometabolismintheagingheart