Histone modifications as molecular drivers of cardiac aging: Metabolic alterations, epigenetic mechanisms, and emerging therapeutic strategies.

Faris Alrumaihi, Amin A Al-Doaiss, Faqir Ullah, Wanian M Alwanian, Hajed Obaid Alharbi, Fai Abdullah Alassaf, Somayah Mohammad Alfifi, Fahad M Alshabrmi, Faris F Aba Alkhay, Eid A Alatawi

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia. · pubmed

Paper

Abstract

Cardiac aging represents a complex pathophysiological process characterized by progressive metabolic recombination and functional dedifferentiation of cardiac cellular components. Despite advancements in cardiovascular medicine, a critical research gap persists in understanding the precise epigenetic mechanisms that drive age-related cardiac dysfunction. This comprehensive review elucidates the pivotal role of histone modifications-including methylation, acetylation, and phosphorylation-in orchestrating the molecular landscape of cardiac aging. Significant gaps remain in our understanding of site-specific histone modification impacts on cardiac function, the intricate crosstalk between different histone marks, and their integration with metabolic alterations that characterize the aging myocardium. Current evidence reveals a dynamic epigenetic signature in aged cardiac tissue, typically featuring increased transcriptional activation markers alongside decreased repressive marks, though context-dependent variations exist. This review explores how histone modifications influence critical pathways governing mitochondrial dysfunction, DNA damage repair, inflammation, and fibrosis in aging hearts. Innovative therapeutic approaches targeting specific histone-modifying enzymes promise to mitigate age-related cardiac deterioration, potentially revolutionizing treatment paradigms for cardiovascular diseases in aging populations. Addressing these knowledge gaps requires multidimensional approaches that integrate epigenomics with functional assessment of cardiac performance.

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Research summary

Histone modifications play a crucial role in the molecular mechanisms of cardiac aging and potential therapeutic strategies. The paper addresses the underlying epigenetic mechanisms contributing to age-related cardiac dysfunction, which is directly relevant to understanding and potentially mitigating the root causes of aging.

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