02234nas a2200397   4500000000100000000000100001008004100002260001500043653002800058653002200086653001500108653001500123653002800138100001500166700001900181700001900200700001600219700001300235700001500248700001400263700001800277700001600295700001900311700001500330700001900345700001700364700001800381700001600399700001300415245007900428856005500507300000900562490000600571520124500577022001401822       2025                            d  c2025-11-0510aAnalytical biochemistry10aBiological models10aBiomarkers10aComplexity10aStem-cell biotechnology1 aInWha Park1 aHyokyeong Gwon1 aYeonjeong Jung1 aBoyoung Kim1 aGaeun Ju1 aEugene Sin1 aHye In An1 aHye Jung Bang1 aTaegwan Yun1 aSeung Hwan Lee1 aWonsik Lee1 aChoon-Gon Jang1 aHyo-Jong Lee1 aChung Sub Kim1 aJeongmi Lee1 aSoah Lee00aIntegrating allostasis and emerging technologies to study complex diseases  uhttps://www.nature.com/articles/s42003-025-08939-3  a15260 v83 aThe study of complex diseases has traditionally relied on reductionist methods, which, although informative, tend to overlook the dynamic interactions and systemic interconnectivity inherent in biological systems. Allostasis, a framework that focuses on physiological adaptations to stress and the maintenance of stability through change, provides a valuable perspective for understanding these diseases. This review summarizes how the allostasis framework defines the cumulative physiological burden—known as allostatic load—imposed by chronic stressors such as persistent psychosocial pressure, drug abuse, and chronic infections. It also explores how adaptive physiological shifts, or changes in allostatic state, contribute to disorders, particularly drug addiction, immune diseases, and cancer. We then review recent studies that uncover stress adaptation mechanisms using cutting-edge technologies, such as multi-omics approaches, induced pluripotent stem cells (iPSCs), and organoid technology. This integrative approach, combining advanced technologies with the allostasis framework, can deepen our understanding of complex disease pathogenesis and inform the development of more effective diagnostic and therapeutic strategies.  a2399-3642