Aging Dis. 2026 May 2. doi: 10.14336/AD.2026.0265. Online ahead of print.
ABSTRACT
Aging is the dominant risk factor for heart failure with preserved ejection fraction (HFpEF), a condition increasingly recognized as a manifestation of maladaptive cardiovascular aging. This review summarizes current evidence linking inflammaging, a chronic, low-grade inflammatory state driven by immunosenescence, mitochondrial dysfunction, and cellular senescence, to progressive myocardial fibrosis, diastolic stiffness, and HFpEF development. We discuss mechanistic pathways connecting fibroblast activation, extracellular matrix remodeling, adipose tissue-driven inflammation, and phenotype-specific inflammatory signatures, as well as the role of multimodality imaging in detecting early fibrotic and inflammatory changes. Finally, we critically evaluate emerging immunometabolic therapies, highlighting the limitations of single-cytokine blockade and the disease-modifying potential of SGLT2 inhibitors and GLP-1 receptor agonists in targeting HFpEF.
PMID:42149096 | DOI:10.14336/AD.2026.0265