Organotypic cultures as aging associated disease models.

Aging remains a primary risk factor for a host of diseases, including leading causes of death. Aging and associated diseases are complex, with numerous contributing factors and phenotypes that occur at the molecular, cellular, and organ levels. Despite the complexity of aging phenomena, models currently used in aging research are very limited. Frequently used animal models, such as mice, often have important physiological differences, age at very different rates, or have genetic modifications that induce disease. On the other hand, routinely used in vitro models lack the complex tissue-scale and systemic cues that are disrupted in aging. To 􀂦ll in gaps between in vivo and traditional in vitro models, researchers have increasingly been turning to more advanced cell culture models, including “organotypic” models, defined as models that partially preserve the cell populations and tissue structure of native tissue. While powerful tools, the development of these models is a 􀂦eld of its own, and many aging researchers may be unaware of recent progress in organotypic models, or hesitant to include these models in their own work. In this review, we describe recent progress in tissue engineering applied to organotypic models, highlighting examples explicitly linked to aging and associated disease, as well as examples of models that are relevant to aging. We also include models with cells derived from stem cell sources. We specifically highlight progress made in skin, gut, and skeletal muscle, and describe how the models have been used for aging studies or similar research. Throughout, this review emphasizes the accessibility of these models and aims to provide a resource for researchers seeking to leverage these powerful tools.