Adaptive homeostasis

Abstract

Homeostasis is a central pillar of modern Physiology. The term homeostasis was invented by Walter Bradford Cannon in an attempt to extend and codify the principle of 'milieu intérieur,' or a constant interior bodily environment, that had previously been postulated by Claude Bernard. Clearly, 'milieu intérieur' and homeostasis have served us well for over a century. Nevertheless, research on signal transduction systems that regulate gene expression, or that cause biochemical alterations to existing enzymes, in response to external and internal stimuli, makes it clear that biological systems are continuously making short-term adaptations both to set-points, and to the range of 'normal' capacity. These transient adaptations typically occur in response to relatively mild changes in conditions, to programs of exercise training, or to sub-toxic, non-damaging levels of chemical agents; thus, the terms hormesis, heterostasis, and allostasis are not accurate descriptors. Therefore, an operational adjustment to our understanding of homeostasis suggests that the modified term, Adaptive Homeostasis, may be useful especially in studies of stress, toxicology, disease, and aging. Adaptive Homeostasis may be defined as follows: 'The transient expansion or contraction of the homeostatic range in response to exposure to sub-toxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events.'

Keywords: Adaptation; Aging; Homeostasis; Hormesis; Nrf2; Oxidative Stress.

Fig 1

Claude Bernard (1813–1878) The celebrated French physiologist who developed concept of milieu intérieur, or a constant interior bodily environment in 1865 (1). Image attribution: https://upload.wikimedia.org/wikipedia/commons/e/e7/Bernard_Claude.jpg

Fig. 2

Walter Bradford Cannon (1871–1945) The Harvard Physiologist who coined the term, Homeostasis in 1926 to describe and extend Bernard’s milieu intérieur concept (2). Homeostasis was subsequently popularized (in 1932) in Cannon’s highly influential book, The Wisdom of the Body (3). Image attribution: https://upload.wikimedia.org/wikipedia/commons/7/78/Walter_Bradford_Cannon_1934.jp

Fig. 3

A Graphic Depiction of the Principle of Homeostasis. According to Arthur C. Guyton’s Textbook of Medical Physiology (10), “The term homeostasis is used by physiologists to mean, maintenance of nearly constant conditions in the internal environment.” Any biological function or measurement, therefore, will oscilate around a mean or median, within a range that is considered a ‘normal’ or physiological.

Fig. 4

A Graphic Representation of Adaptive Homeostasis. Here, in addition to the normal or physiological range, are added both positive and negative adaptive ranges that can be transiently induced via signal transduction pathways in response to sub-toxic, non-damaging, stimuli. Thus, for example, a signal given by nanomolar levels of H₂O₂ can act via the Keep1-Nrf2 system to increase synthesis of protective levels of proteasome, immunoproteasome, and Pa28 (or 11S) proteasome regulator for a period of several hours (–36): an example of positive Adaptive Homeostasis. Loss of the H₂O₂ stimulus then returns the system to the basal homeostatic range. Similarly, when organisms are exposed to a diet rich in amino acids, they turn off production of amino acid synthetases, thus decreasing capacity to synthesize amino acids: an example of Negative Homeostasis. Restoration of a ‘normal’ diet would then reverse the transient decrease in capacity back within the normal homeostatic range.