The aging interactome: From cellular dysregulation to therapeutic frontiers in age-related diseases

Biological aging is a complex, multifaceted process characterized by the progressive erosion of cellular homeostasis, driven by intersecting pathways of inflammaging, immune senescence, mitochondrial dysfunction, and genomic instability. This review delineates current knowledge on the interconnected mechanisms underlying aging-related diseases, including atherosclerosis, obesity, sarcopenia, neurodegenerative disorders, rheumatoid arthritis, and cancer. We further discuss the critical role of contributing factors such as microbiome dysbiosis, sex differences, and exosome-mediated communication in modulating disease progression. Advancements in multi-omics technologies and AI-driven biomarkers, particularly epigenetic clocks, are highlighted for their ability to precisely quantify biological aging and stratify disease risk. Finally, we explore the therapeutic potential and promising clinical trials of targeting these shared mechanisms with senolytics, mitochondrial enhancers, and immunomodulators, offering a paradigm shift from disease-specific treatment to holistic interventions designed to extend healthspan. © 2025 Elsevier B.V., All rights reserved.