o:38468 Modeling aging in a culture dish: towards the development of more sophisticated in vitro models of human skin aging en ABSTRACT With age, human skin undergoes a progressive decline in essential functions, including barrier protection, immunity, and wound healing capacity, which underlie many age-related skin diseases. Skin aging is not only driven by chronological aging, but also strongly influenced by extrinsic stressors, notably ultraviolet radiation, pollutants, and diet. Thus, understanding the complex interplay between these intrinsic and extrinsic factors is essential for developing strategies to preserve skin health across the lifespan. Given the growing appreciation for the physiologic differences between humans and animal models, more advanced in vitro and ex vivo models are needed to dissect the human-specific mechanisms of skin aging and test emerging therapies. In this review, we summarize the major hallmarks of human skin aging and provide an overview of current in vitro modeling approaches that capture both intrinsic and environmental aging mechanisms. Aging; Human skin; In vitro models; Organotypic; Senescence; Skin equivalent 1552099 DOI: 10.1016/j.arr.2026.103109 2026-03-26T09:19:32.384Z 44 yes 46 Stefania Briganti Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomic Research, San Gallicano Dermatological Institute IRCCS, Rome, Italy Emanuela Camera Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomic Research, San Gallicano Dermatological Institute IRCCS, Rome, Italy person Jesús Ciriza Tissue Microenvironment (TME) Lab, Aragon Institute for Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Zaragoza, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain person Estibaliz Fernandez Carro Tissue Microenvironment (TME) Lab, Aragon Institute for Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain person Milica Jovanović Krivokuća Department of Reproductive Biology, Institute for Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia doktor bioloških nauka person 0000-0001-8292-4853 Jerome Lamartine Laboratory of Tissue Biology and Therapeutic Engineering (LBTI) CNRS UMR5305 University Claude Bernard Lyon I, Lyon, France person Sophia Letsiou Department of Food Science and Technology, University of West Attica, Athens, Greece person Mirjana Nacka-Aleksić Department of Reproductive Biology, Institute for Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia doktor medicinskih nauka-farmacija person 0000-0003-0750-9347 Carien M Niessen Department Cell Biology of the Skin, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Center for Molecular Medicine Cologne, University Hospital Cologne, University of Cologne, Cologne, Germany person Núria Oliva Bioengineering Department, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain person Andrea Pirković Department of Reproductive Biology, Institute for Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia doktor bioloških nauka person 0000-0002-1182-4895 Markus Schosserer Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria person Desmond J Tobin The Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Ireland person Maria Cavinato Division of Cellular Senescence in Aging and Disease, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biosciences Innsbruck, Innsbruck, Austria person John T Connelly Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom person application/pdf 82015 https://phaidrabg.bg.ac.rs/o:38468 no yes 16 70 92000002 11A29 11A2901 Ageing Research Reviews Elsevier, Netherlands 2026