Aging is a priority for health systems in Western countries, particularly because of its link to chronic diseases such as heart failure. The present research project aims to explore the molecular mechanisms of chronic inflammation in heart failure during aging, with a focus on preserved ejection fraction decompensation (HFpEF), a phenotype highly prevalent in the elderly. The study takes a multidisciplinary approach involving clinicians, cardiologists, biologists, and bioinformaticians, leveraging innovative Network Medicine methodologies and integrating clinical, epigenomic, proteomic, and environmental lifestyle data. The main objective is to conduct a large-scale epigenome-wide association study (EWAS) to analyze DNA methylation changes in circulating CD4+ and CD8+ T cells from the healthy young subject to the elderly with HFpEF. The identification of epigenetic markers associated with risk factors and diseases may clarify the role of epigenetic regulation in pathophysiology and open new perspectives for prevention, diagnosis, and treatment strategies. Methylomes will be analyzed within a Network Medicine framework, with construction of an inflammasome-focused interactome and integration with targeted proteomics based on 96 validated inflammatory biomarkers. Antigenic phenotyping will complement the epigenomic analysis, allowing the identification of epigenetically sensitive pro-inflammatory biomarkers throughout the developmental pathway to HFpEF. A secondary goal is the development of a simple and scalable panel of epigenetic biomarkers for early identification of decompensation in the elderly, potentially applicable directly at the patient's bedside for personalized risk stratification. The project also has social relevance, promoting awareness of healthy aging among the elderly population.