02796nas a2200241   4500000000100000008004100001260001500042653001000057653002700067653002300094653003100117653002000148653001400168100001400182700001700196700001500213245011900228856007200347300001100419490000800430520210200438022001402540       2025                            d  c2025-05-0110aaging10aAging-related diseases10aGeriatric diseases10amicrophysiological systems10aorgan-on-a-chip10aorganoids1 aChao Song1 aJiachen Yang1 aZhongze Gu00aLatest developments of microphysiological systems (MPS) in aging-related and geriatric diseases research: A review  uhttps://www.sciencedirect.com/science/article/pii/S1568163725000741  a1027280 v1073 aAging is a gradual and irreversible process accompanied by the decline in tissue function and a significantly increased risk of various aging-related and geriatric diseases. Especially in the paradoxical context of accelerated global aging and the widespread emergence of pandemics, aging-related and geriatric diseases have become leading causes of individual mortality and disability, drawing increasing attention from researchers and investors alike. Despite the utility of current in vitro systems and in vivo animal models for studying aging, these approaches are limited by insurmountable inherent constraints. In response, microphysiological systems (MPS), leveraging advances in tissue engineering and microfluidics, have emerged as highly promising platforms. MPS are capable of replicating key features of the tissue microenvironment within microfabricated devices, offering biomimetic tissue culture conditions that enhance the in vitro simulation of intact or precise human body structure and function. This capability improves the predictability of clinical trial outcomes while reducing time and cost. In this review, we focus on recent advancements in MPS used to study age-related and geriatric diseases, with particular emphasis on the application of organoids and organ-on-a-chip technologies in understanding cardiovascular diseases, cerebrovascular diseases, neurodegenerative diseases, fibrotic diseases, locomotor and sensory degenerative disorders, and rare diseases. And we aim to provide readers with critical guidelines and an overview of examples for modeling age-related and geriatric diseases using MPS, exploring mechanisms, treatments, drug screening, and other subsequent applications, from a physiopathological perspective, emphasizing the characteristic of age-related and geriatric diseases and their established correlations with the aging process. We also discuss the limitations of current models and propose future directions for MPS in aging research, highlighting the potential of interdisciplinary approaches to address unresolved challenges in the field.  a1568-1637