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Publications

Journal Article Review Ahead of print

PubMed: 41876067 DOI: 10.1016/j.arr.2026.103109

Modeling aging in a culture dish: towards the development of more sophisticated in vitro models of human skin aging.

Ageing Res Rev

Authors: Stefania Briganti, Emanuela Camera, Jesús Ciriza, Estibaliz Fernandez Carro, Milica Jovanović Krivokuća, Jerome Lamartine, Sophia Letsiou, Mirjana Nacka-Aleksić, Carien M Niessen, Núria Oliva, Andrea Pirkovic, Markus Schosserer, Desmond J Tobin, Maria Cavinato, John T Connelly

Affiliations

  • Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomic Research, San Gallicano Dermatological Institute IRCCS, Rome, Italy.
  • 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.
  • Tissue Microenvironment (TME) Lab, Aragon Institute for Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
  • Department of Reproductive Biology, Institute for Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia.
  • Laboratory of Tissue Biology and Therapeutic Engineering (LBTI) CNRS UMR5305 University Claude Bernard Lyon I, Lyon, France.
  • Department of Food Science and Technology, University of West Attica, Athens, Greece.
  • 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.
  • Bioengineering Department, Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, Spain.
  • Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria.
  • The Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Ireland.
  • 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.
  • Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom.

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. We highlight recent advances in complex 3D in vitro systems - including full-thickness human skin equivalents, organoids, and microphysiological platforms - and discuss how these emerging models can be leveraged to interrogate aging biology and support translational research. Together, these developments pave the way for more predictive and mechanistically informed tools to study skin aging and to accelerate the development of next-generation therapeutic and preventive strategies.

MeSH

Skin, Aging, Skin Diseases, Skin Aging, Therapeutics