Three-Body Problem in Stress Biology: Balance between O2, NO, and H2S in the Context of Hans Selye’s Stress Concept

Hans Selye’s stress concept, first introduced in the 1930s, has undergone substantial evolution, extending beyond biology and medicine to influence diverse academic dis-ciplines. Initially, Selye’s General Adaptation Syndrome (GAS) described nonspecific physiological responses to stressors exclusively in mammals, without addressing other biological systems. Consequently, the concept of stress developed independently in bi-ology and medicine, shaped by distinct physiological contexts. This review provides a historical overview of stress research, highlights both parallels and divergences in stress responses between plants and animals, and integrates insights from traditional Eastern philosophies. We propose an updated GAS framework that incorporates the dynamic balance among reactive oxygen species (ROS), reactive nitrogen species (RNS), and re-active sulfur species (RSS) within the broader context of oxidative stress. To achieve a holistic understanding of nonspecific responses to diverse stressors, we discuss that ion-otropic glutamate receptors (iGluRs)—including N-methyl-D-aspartate receptors (NMDARs) in animals, glutamate receptor-like channels (GLRs) in plants, and the evolutionarily conserved transient receptor potential (TRP) channel superfamily—may represent a minimal molecular framework underlying Selye’s GAS. This perspective expands the classical stress paradigm, providing new insights into redox biology, in-terspecies stress adaptation, and evolutionary physiology.