o:3333 Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology en The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging. Humans; Cellular Senescence Drug Effects; Metabolic Networks and Pathways; Animals; Chronic Disease; Inflammation Metabolism Immunology; Lung Diseases Etiology Drug Therapy Metabolism Immunology; Pulmonary Disease, Chronic Obstructive Metabolism Drug Therapy Immunology; Aging Immunology Metabolism 1552099 10.1111/all.15977 2024-08-08T12:27:19.759Z 44 yes 46 Franziska Roth-Walter University of Veterinary Medicine, Vienna / Medical University of Vienna 0000-0001-5005-9228 I. M. Adcock Imperial College London person 0000-0003-2101-8843 C. Benito-Villalvilla Universidad Complutense de Madrid person 0000-0002-5544-0199 Rodolfo Bianchini University of Veterinary Medicine Vienna person 0000-0003-0351-6937 L. Bjermer Lund University person 0000-0002-3441-8099 G. Caramori University of Parma person 0000-0002-9807-327X L. Cari University of Perugia person 0000-0003-0698-3872 K. F. Chung Imperial College London person 0000-0001-7101-1426 Z. Diamant Skåne University Hospital / Charles University / University of Groningen person 0000-0003-0133-0100 I. Eguiluz-Gracia Instituto de Investigación Biomédica de Málaga person 0000-0002-3774-931X E. F. Kohl University Medical Center Utrecht person 0000-0001-7368-9820 M. Jesenak Comenius University Bratislava person 0000-0001-7976-2523 F. Levi-Schaffer Hebrew University of Jerusalem person G. Nocentini University of Perugia person 0000-0002-5209-0488 L. O'Mahony University College Cork person 0000-0003-4705-3583 O. Palomares Universidad Complutense de Madrid person 0000-0003-4516-0369 F. Redegeld Utrecht University person 0000-0001-8830-7960 M. Sokolowska University of Zurich / CK-CARE person 0000-0001-9710-6685 B. C. A. M. Van Esch Utrecht University person 0000-0001-9961-750X C. Stellato University of Salerno person 0000-0002-1294-8355 application/pdf 2129791 https://phaidra.vetmeduni.ac.at/o:3333 no yes 17 70 1552253 Allergy 34 79 5 1089 1122 Wiley 2023