Interferon-related inflammaging links epigenetic age acceleration to multimorbidity.

Zhaoli Liu, Athanasios Ziogas, Yihan Zhang, Manoj Kumar Gupta, Konstantin Föhse, Esther Taks, Elisabeth Dulfer, Andrei Sarlea, Lorenzo Ventriglia, Büsra Geckin, Mohamad Ballan, Nienke van Unen, Leonie Helder, Stephanie Trittel, Peggy Riese, Simone Moorlag, Charlotte de Bree, Valerie Koeken, Vera Mourits, Martin Jaeger, Frank Pessler, Carlos A Guzmán, Leo A B Joosten, Yang Li, Cheng-Jian Xu, Mihai G Netea

Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; TWINCORE, a Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, China. · pubmed

Paper

Abstract

Chronic systemic inflammation and DNA methylation changes are two major hallmarks of aging, yet their interaction is poorly known. We investigated the relation between circulating inflammatory proteome and epigenetic age acceleration as assessed by DNA methylation in four independent cohorts of different ages and health conditions. Epigenetic age scores known to predict human health span (GrimAge and PhenoAge) were more strongly associated with age-associated inflammatory proteins, frailty, and multimorbidity when compared to epigenetic age scores associated with lifespan (Horvath and Hannum). Mendelian randomization analyses showed that blood concentrations of important inflammatory cytokines associated with the interferon pathway (CXCL9, CXCL10, CCL11, and IL-18) increase with age and are causal drivers of epigenetic age acceleration and age-related diseases. Furthermore, aging was associated with dysregulation of cytokine production capacity in immune cells in response to microbial stimulation. These findings argue that the interferon pathway may represent a target for anti-aging interventions.

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Research summary

The paper claims that the interferon pathway is a causal driver of epigenetic age acceleration and age-related diseases. This research explores the interaction between chronic inflammation and epigenetic changes, addressing potential root causes of aging and suggesting targets for anti-aging interventions.

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