CHIP In Cardiovascular And Immune Ageing.

Authors

Harish C Chandramoorthy, Muhammad Afzal, Haider Ali, Kavita Goyal, Vikas Jakhmola, Gaurav Gupta, Ayidh Mohammed Safar Alsalem, Kumarappan Chidambaram

Published in

Ageing research reviews. Pages 103214. Jun 24, 2026. Epub Jun 24, 2026.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) describes the proliferation of blood cell clones that carry driver mutations, such as DNA methyltransferase 3 alpha (DNMT3A), ten-eleven translocation 2 (TET2), additional sex combs like 1 (ASXL1), and Janus kinase 2 (JAK2), without leading to any obvious malignancy. Its occurrence rate is age-related and associated with cardiovascular and immune aging. In prospective cohort studies, CHIP substantially elevated the risk of myocardial infarction, stroke, and heart failure, with a relative risk increase ranging from 1.4 to 2.0-fold. Furthermore, a larger clone size, as indicated by the variant allele fraction (VAF), is correlated with a heightened risk. Both experimental and human evidence support the association of proinflammatory myeloid reprogramming with the loss of ten-eleven translocation 2 (TET2)/DNA methyltransferase 3 alpha (DNMT3A), NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) signaling, as well as endothelial dysfunction and atherothrombosis. However, the effect sizes vary depending on the specific gene, tissue, and context, and residual confounding remains a concern. This paper reviews the epidemiology and pathophysiology of the disease, its clinical utility, including indications for testing, interpretation of variants, VAF levels, and the added value to conventional risk models and treatment methods, such as cytokine- and mutation-based approaches. Priority areas include genotype- and VAF-stratified trials that focus on outcomes relevant to aging and are rigorously monitored for their safety. Overall, CHIP is associated with somatic mosaicism, inflammaging, and aging of the cardiovascular and immune systems, although significant questions regarding causation and actionability remain unresolved.

PMID:
42342158
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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