Homestasis vs Allostasis
Homeostasis (HM) is a long-debated concept in the field of neuroscience and immunology. The term was originally coined by Cannon, who defined it as “a condition - a condition which may vary, but which is relatively constant”. Recently, McEwen has provided a more comprehensive definition of HM, explaining it as the return to a predetermined set of physiological conditions of equilibrium of the body, following stress. Of note is the fact that both authors refer to HM as a return to equilibrium, rather than an immobile state of the system.
The semantic debate over HM has intensified since the introduction of the concept of allostasis by Sterling and Eyers. They claimed that the term HM is misleading, and that instead the body must respond to environmental stressors by altering all the baseline parameters through a process of allostasis. In their original article, HM was interpreted as a state of static equilibrium, rather than a process that allowed a return to baseline parameters, as postulated by Cannon. In their description, allostasis encompasses both baseline physiological parameters necessary for survival, and the dynamic mechanisms needed to maintain them over time.
In order to help solve this historical debate, McEwen offered a unifying model of HM and allostasis, whereby allostasis is complementary to HM and is the process that maintains HM through dynamically-changing physiological parameters (eg. blood pressure and heart rate), to respond to environmental demands. In his model, HM refers to the stability of core tissue parameters, such as pH and temperature, while allostasis dynamically modifies pericellular parameters (eg. blood pressure and oxygen) to maintain the core parameters stable (HM) over time. Importantly, he explained that, differently from HM that is the basis of survival, allostasis is a process that allows adaptation over time. The two terms have been interchangeably used in the literature, even to this day. In this review we will use the following definitions of HM and allostasis: + Homeostasis is the return to predetermined healthy baseline biological parameters (both core tissue and pericellular), such as pH of 7, body temperature of ~37℃, blood oxygen at 99% etc. HM is important for survival + Allostasis refers to processes that respond to environmental (internal/external) challenges by altering pericellular physiological parameters, so as to maintain HM over time. Allostasis is important for adaptation.
The body enters an allostatic state when allostasis has been active for a long period of time, and thus the mediators are deviated from their normal levels to a new set point, that can be lower or higher than the normal one. Being in an allostatic state comes at a cost to the body, especially when responding to chronic stressors that prevent the stress response from turning off. Over time, exposure to multiple stressors (eg. demands of daily routines, injury, disease, age etc) lead to changes in the mediator, and ultimately, physiological parameter levels, culminating in a cumulative effect on the stress response called allostatic load (AL). AL is reached through one of four possible responses:
repeated novel stressors cause spikes in mediator levels;
failure to adapt to the same stressor;
failure to turn off the stress response;
overactive responses. The physical repercussions of AL manifest in a general sense of being ‘stressed out’, resulting in fatigue, anger and frustration among others. A prolonged dysregulated condition of allostasis often results in an extreme state for the body, called allostatic overload (AOL) (Fig.1). Differently from AL, AOL is more chronic and intense in nature, and reflects the transition from normal wear-and-tear caused by daily demands, to a significant disruption of health, such as onset of diabetes or obesity.
Figure 1. Homeostasis, allostasis and dysregulated response. The diagram shows two scenarios: 1) a normal response where the body is subject to acute stressors and allostasis is able to restore homeostasis; 2) a dysregulated response where repeated acute or chronic stressors cause a prolonged allostatic state, leading to allostatic load and overload.
Although the terms AL and AOL are often mentioned in biomedical literature, there are no formal quantitative definitions for the two concepts. In particular, AOL is used to express extreme dysregulation of the stress response, but no “threshold” for when the body enters this phase has been proposed.
Supposedly, this is because the circumstances in which AOL is triggered vary significantly from one individual to the next, and a stressor may not result in AOL in all cases. A further challenge with setting thresholds is that there is lack of agreement over what to measure to determine AL/AOL: are particular mediators and levels (eg. cortisol and other hormones) enough, or should we also consider contributing variables (eg. age, gender, diet, habitat, health behaviours)? The issue with these arbitrary definitions is that many studies then identify genetic makeup as the leading cause for complex diseases such as depression, rather than dysregulation from chronic exposure to stressors.
Below we clarify the timeline of events from HM to AOL along with likely outcomes of AL and AOL. Fig.2 indicates that AOL is the moment when disease onset begins, where no return to homeostasis is possible and a new “baseline” for the body has been created by shifting the optimal baseline homeostasis parameters (eg. blood pressure etc). Of note is the fact that the new baseline under AOL does not equate HM, instead is an unhealthy dysregulated baseline caused by persistent exposure to stress.
It could be argued that AL happens even when humans adapt to harsh environments (eg. really cold climates) and, as a result, the baseline parameters may change. The important distinction is that engagement of AL in individuals moving to the North Pole, eventually changing their baseline parameters, is a natural phenomenon of adaptation and evolution.
Instead, exposure to high air pollution is an artificial result of human activity that results in unadapted baseline parameters and disease. Nature should determine what the human body is subjected to, not human activity. This difference can be better explained by looking at wildlife species. Extinction of species is an event driven by natural selection, but in recent decades widespread mass extinctions have been taking place as a result of human activity: this unnatural selection is being applied to communities of our society.
Figure 2. Timeline of allostasis. The diagram shows the short-term (hours/days) action of allostasis to restore homeostasis; allostatic load happens when allostasis is engaged for more prolonged periods (months/ few years) causing feelings commonly termed as stress or low immune defences; finally chronic and persistent exposure to stressors and in a state of allostatic load lead to overload and thus disease onset.
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