Eur J Immunol. 2026 Jul;56(7):e70239. doi: 10.1002/eji.70239.
ABSTRACT
Inflammaging, defined as the persistent, low-grade sterile inflammation accompanying aging, represents a central driver of age-related pathology, including cardiovascular dysfunction, neurodegeneration, metabolic disorders, and frailty. This review discusses the most recent advances in understanding its mechanistic basis, encompassing cellular senescence, the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, immune cell senescence, innate immune hyperactivation, defective inflammatory resolution, and nutrient-sensing dysregulation. Single-cell and spatial transcriptomics reveal tissue-specific and context-dependent patterns, highlighting the systemic complexity of inflammaging. Preclinical interventions demonstrate that inflammaging is modifiable through senolytics, which selectively eliminate senescent cells, and senomorphics, which suppress SASP without inducing cell death. Metabolic modulators such as metformin and rapamycin attenuate inflammatory signaling, while immune-directed therapies and microbiome-targeted interventions provide synergistic benefits through combinatorial approaches. Early-phase clinical trials in frail older adults show feasibility, safety, and preliminary efficacy, including reductions in circulating inflammatory markers, improved physical function, and enhanced immune responsiveness. Inflammaging trajectories are shaped by lifestyle, environmental exposures, and evolutionary factors, underscoring the need for personalized interventions. Remaining challenges include biomarker development, long-term safety evaluation, and heterogeneity across aging populations. Addressing these through interdisciplinary research supports a precision geroscience paradigm, where multimodal targeting of inflammaging can extend healthspan and reduce chronic disease burden.
PMID:42502879 | DOI:10.1002/eji.70239