Department of Pathophysiology, University of Zagreb School of Medicine, Kispaticeva 12, 10 000 Zagreb, Croatia.
Department of Pathophysiology, University Hospital Center Zagreb - KBC Rebro, Kispaticeva 12, 10 000 Zagreb, Croatia.
Redox Biol. 2017 Oct;13:235-243. doi: 10.1016/j.redox.2017.05.008. Epub 2017 May 18.
Finite disarrangements of important (vital) physiological agents and nutrients can induce plethora of beneficial effects, exceeding mere attenuation of the specific stress. Such response to disrupted homeostasis appears to be universally conserved among species. The underlying mechanism of improved fitness and longevity, when physiological agents act outside their normal range is similar to hormesis, a phenomenon whereby toxins elicit beneficial effects at low doses. Due to similarity with such non-linear response to toxins described with J-shaped curve, we have coined a new term "mirror J-shaped curves" for non-linear response to finite disarrangement of physiological agents. Examples from the clinical trials and basic research are provided, along with the unifying mechanisms that tie classical non-linear response to toxins with the non-linear response to physiological agents (glucose, oxygen, osmolarity, thermal energy, calcium, body mass, calorie intake and exercise). Reactive oxygen species and cytosolic calcium seem to be common triggers of signaling pathways that result in these beneficial effects. Awareness of such phenomena and exploring underlying mechanisms can help physicians in their everyday practice. It can also benefit researchers when designing studies and interpreting growing number of scientific data showing non-linear responses to physiological agents.
有限的重要（生命）生理因子和营养素的紊乱可以诱导大量有益的效果，超过单纯的特定应激的衰减。这种对平衡破坏的反应似乎在物种间普遍存在。当生理因子作用于其正常范围之外时，改善适应性和长寿的潜在机制与毒物兴奋效应相似，即在低剂量下毒物会产生有益的效果。由于与描述为 J 形曲线的非线性对毒素的这种类似反应，我们为生理因子的有限紊乱的非线性反应创造了一个新术语“镜像 J 形曲线”。提供了来自临床试验和基础研究的例子，以及将经典的非线性对毒素的反应与非线性对生理因子（葡萄糖、氧气、渗透压、热能、钙、体重、热量摄入和运动）的反应联系起来的统一机制。活性氧和细胞质钙似乎是导致这些有益效果的信号通路的共同触发因素。意识到这些现象并探索潜在机制可以帮助医生在日常实践中。当研究人员设计研究和解释越来越多的显示生理因子的非线性反应的科学数据时，这也可能对他们有帮助。
