Principles of Allostasis: Optimal Design, Predictive Regulation, Pathophysiology, and Rational Therapeutics

Sterling, Peter

doi:10.1017/cbo9781316257081.004

Cited by 256 publications

(369 citation statements)

References 91 publications

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“…The present data offer little grounds to prefer one mode of happiness over the other based on affective experience, but they identify a stark contrast at the level of molecular physiology. If "the good life" is a long and healthy life free from the allostatic load of chronic stress, threat, and uncertainty (55,56), CTRA gene expression may provide a negative reference point for how not to live [figuratively in its association with adverse experience (12,33) and literally in its expression of disease-promoting genes (37)]. If we ask which type of happiness most directly opposes that molecular antipode, a functional genomic perspective favors eudaimonia.…”

Section: Discussionmentioning

confidence: 99%

A functional genomic perspective on human well-being

Fredrickson

Grewen

Coffey

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

396

444

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To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences.

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Section: Discussionmentioning

confidence: 99%

A functional genomic perspective on human well-being

Fredrickson

Grewen

Coffey

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

396

444

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“…The concept of allostasis was introduced in 1988 in part to account for such lifestyle diseases and dysfunctional physiological states that develop under a sustained burden of stressors (Sterling and Eyer 1988;Sterling 2004). Although the validity of the claimed differences between allostasis and homeostasis has been energetically debated (McEwen 1998;McEwen and Wingfield 2003;Woods and Ramsay 2007;Booth 2008;Cooper 2008;Romero et al 2009;Koolhaas et al 2011;Sterling 2012;Ramsay and Woods 2014), the discussion has drawn attention to important aspects of physiological regulation and to changes that occur during adaptation (acclimatisation) of the individual to environmental conditions and during chronic stress.…”

Section: Effects From Underload and Overload By Environmental Stimulimentioning

confidence: 99%

Resilience in farm animals: biology, management, breeding and implications for animal welfare

2016

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Abstract.A capacity for the animal to recover quickly from the impact of physical and social stressors and disease challenges is likely to improve evolutionary fitness of wild species and welfare and performance of farm animals. Salience and valence of stimuli sensed through neurosensors, chemosensors and immunosensors are perceived and integrated centrally to generate emotions and engage physiological, behavioural, immune, cognitive and morphological responses that defend against noxious challenges. These responses can be refined through experience to provide anticipatory and learned reactions at lower cost than innate less-specific reactions. Influences of behaviour type, coping style, and affective state and the relationships between immune responsiveness, disease resistance and resilience are reviewed. We define resilience as the capacity of animals to cope with short-term perturbations in their environment and return rapidly to their pre-challenge status. It is manifested in response to episodic, sporadic or situation-specific attributes of the environment and can be optimised via facultative learning by the individual. It is a comparative measure of differences between individuals in the outcomes that follow exposure to potentially adverse situations. In contrast, robustness is the capacity to maintain productivity in a wide range of environments without compromising reproduction, health and wellbeing. Robustness is manifested in response to persistent or cyclical attributes of the environment and is effected via activity of innate regulatory pathways. We suggest that for farm animals, husbandry practices that incorporate physical and social stressors and interactions with humans such as weaning, change of housing, and introduction to the milking parlour can be used to characterise resilience phenotypes. In these settings, resilience is likely to be more readily identified through the rate of return of variables to pre-challenge or normal status rather than through measuring the activity of diverse stress response and adaptation mechanisms. Our strategy for phenotyping resilience of sheep and cattle during weaning is described. Opportunities are examined to increase resilience through genetic selection and through improved management practices that provide emotional and cognitive enrichment and stress inoculation.Additional keywords: affective state, allostasis, animal behaviour, animal temperament, animal welfare, disease resistance, genetic selection, homeostasis, resilience, robustness, stress inoculation.

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“…Some authors (e.g. Schulkin, 2003;Sterling, 2004) have emphasized how the central coordination of physiology, anticipatory physiological responses, and the interplay of physiology and behaviour appear to be given short shrift by the classic homeostatic paradigm of physiological regulation. The concept of allostasis , defined as the "...process by which an organism achieves internal viability through bodily changes of state" has been proposed as an alternative (Schulkin, 2003;p.…”

Section: Importance Of Anticipatory Responses In Regulatory Physiologymentioning

confidence: 99%

Anticipatory physiological regulation in feeding biology: Cephalic phase responses

2008

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Anticipatory physiological regulation is an adaptive strategy that enables animals to respond faster to physiologic and metabolic challenges. The cephalic phase responses are anticipatory responses that prepare animals to digest, absorb and metabolize nutrients. They enable the sensory aspects of the food to interact with the metabolic state of the animal to influence feeding behavior. The anticipatory digestive secretions and metabolic adjustments in response to food cues are key adaptations that affect digestive and metabolic efficiency and aid in controlling the resulting elevation of metabolic fuels in the blood. Cephalic phase responses enable digestion, metabolism and appetite to be regulated in a coordinated fashion. These responses have significant effects on meal size. For example, if the cephalic phase insulin response is blocked the result is poor glucose control and smaller meals. Cephalic phase responses also are linked to motivation to feed, and may play a more direct role in regulating meal size beyond the permissive one of ameliorating negative consequences of feeding. For example, the orexigenic peptide ghrelin appears to display a cephalic phase response, rising before expected meal times. This anticipatory ghrelin response increases appetite; interestingly it also enhances fat absorption, linking appetite with digestion and metabolism.

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Principles of Allostasis: Optimal Design, Predictive Regulation, Pathophysiology, and Rational Therapeutics

Abstract: IN: Allostasis, Homeostasis, and the Costs of Adaptation J. Schulkin Cambridge University Press 20041 Principles of allostasis: optimal design, predictive regulation, pathophysiology and rational therapeutics.

Cited by 256 publications

References 91 publications

A functional genomic perspective on human well-being

A functional genomic perspective on human well-being

Resilience in farm animals: biology, management, breeding and implications for animal welfare

Anticipatory physiological regulation in feeding biology: Cephalic phase responses

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