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Principles of Allostasis: Optimal Design, Predictive Regulation, Pathophysiology, and Rational Therapeutics
Abstract
INTRODUCTION This chapter compares two alternative models of physiological regulation. The first model, homeostasis (“stability through constancy”), has dominated physiology and medicine since Claude Bernard declared, “All the vital mechanisms … have only one object – to preserve constant the conditions of … the internal environment.” His dictum has been interpreted literally to mean that the purpose of physiological regulation is to clamp each internal parameter at a “setpoint” by sensing errors and correcting them with negative feedback (Fig. 1.1; Cannon, 1935). Based on this model, physicians reason that when a parameter deviates from its setpoint value, some internal mechanism must be broken. Consequently, they design therapies to restore the “inappropriate” value to “normal.” The homeostasis model has contributed immeasurably to the theory and practice of scientific medicine, so to criticize it might almost seem absurd. Yet all scientific models eventually encounter new facts that do not fit, and this is now the case for homeostasis. In physiology, evidence accumulates that parameters are not constant. Their variations, rather than signifying error, are apparently designed to reduce error. In medicine, major diseases now rise in prevalence, such as essential hyper-tension and type 2 diabetes, whose causes the homeostasis model cannot explain. For in contrast to the hypertension caused by a constricted renal artery and the diabetes caused by immune destruction of insulin-secreting cells, these newer disorders present no obviously defective mechanism. Treating them with drugs to fix low-level mechanisms that are not broken turns out not to work particularly well. The chapter expands on each of these points. The second model, allostasis (“stability through change”), takes virtually the opposite view. It suggests that the goal of regulation is not constancy, but rather fitness under natural selection. Fitness constrains regulation to be efficient, which implies preventing errors and minimizing costs. Both needs are best accomplished by using prior information to predict demand and then adjusting all parameters to meet it (Fig. 1.1).
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“Stress can harm health, especially when it is prolonged (Sapolsky 2004, Sterling 2004, Taylor 2010).”
From The Psychology of Change: Self-Affirmation and Social Psychological Intervention (2014) · cites this paper as Sterling 2004
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“More generally, psychological threat can increase appetite for sugary and high-fat comfort foods”
From The Psychology of Change: Self-Affirmation and Social Psychological Intervention (2014) · cites this paper as Sterling 2004
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“Vigilance may help explain why various afflictions-poor sleep, obesity, hypertension, heart disease-cluster among distressed populations (Sterling 2004; see also Walton & Cohen 2011).”
From The Psychology of Change: Self-Affirmation and Social Psychological Intervention (2014) · cites this paper as Sterling 2004
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“The most effective way to do so is to change the social environment-classrooms, work, home, society-so that it better provides everyday opportunities to manifest adequacy, such as through meaningful work and civic engagement (Sterling 2004).”
From The Psychology of Change: Self-Affirmation and Social Psychological Intervention (2014) · cites this paper as Sterling 2004
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“As the master regulator of allostasis, the CNS continuously monitors somatic systems, adjusting physiological parameters in response to perturbations and, based upon lifetime experiences, learns to anticipate stressors and to make allostatic adjustments in advance”
From Allostatic load and biological anthropology (2017) · cites this paper as Sterling, 2004
In the citing paper
“Over time, however, it has been recognized that many physiological systems are not regulated so narrowly.In fact, some systems require continual adjustments to maintain optimal current function”
From Allostatic load and biological anthropology (2017) · cites this paper as Sterling, 2004
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Metadata
- Authors
- Sterling, P.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Sterling, Peter
- ORCID
- Sterling, Peter
- Venue
- Allostasis, Homeostasis, and the Costs of Physiological Adaptation
- Publisher
- Cambridge University Press
- Published
- 2004-10-25
- Pages
- 17-64
- OpenAlex
- W2303400061
- Cited by
- 353
- References
- 98
- Citations by year
- 2026: 7 · 2025: 35 · 2024: 17 · 2023: 21 · 2022: 9 · 2021: 18 · 2020: 15 · 2019: 27 · 2018: 14 · 2017: 19 · 2016: 20 · 2015: 22 · 2014: 22 · 2013: 17 · 2012: 22
- FWCI
- 13.11
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Cambridge University Press eBooks (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Health Professions › General Health Professions › Health, psychology, and well-being
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Medicine, History, and Philosophy
- Keywords
- allostasis, homeostasis, physiological regulation, set point, negative feedback, essential hypertension, type 2 diabetes, pathophysiology, rational therapeutics, internal environment
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