Engineering Aging: Approaches to Model and Deconstruct Biological Complexity

The disparity between the global increase in life expectancy and the steady decline in health outcomes with age has been a major driver for developing new ways to research aging. Although this current tools for studying aging outside of the human body-such as animal models and cells in a dish-have improved this fundamental understanding of the markers and key mechanisms underlying this process, several limitations remain. Animal models are poor biological representations of humans and have a weak track record of translating pre-clinical results into successful clinical applications. Similarly, current 2D cellular models do not recapitulate the dynamic 3D environment of human tissue. This gap between the need for accurate biological mimicry and the limitations of current aging models presents an exciting opportunity for the field of biofabrication. Over the past decade, the combination of biofabrication and advanced biomaterials has shown potential to engineer high-resolution features that change over time or respond to specific stimuli. In this perspective, the current state of in vitro aging models is reflected, identify the key features that new models must emulate, discuss the technologies available to meet these complex specifications, and consider some of the potential challenges facing the field.