Future medicine: from molecular pathways to the collective intelligence of the body

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 687 - 710

Published: July 20, 2023

The remarkable anatomical homeostasis exhibited by complex living organisms suggests that they are inherently reprogrammable information-processing systems offer numerous interfaces to their physiological and problem-solving capacities. We briefly review data suggesting the multiscale competency of forms affords a new path for biomedicine exploits innate collective intelligence tissues organs. concept tissue-level allostatic goal-directedness is already bearing fruit in clinical practice. sketch roadmap towards 'somatic psychiatry' using advances bioelectricity behavioral neuroscience design methods induce self-repair structure function. Relaxing assumption cellular control mechanisms static, exploiting powerful concepts from cybernetics, science, developmental biology may spark definitive solutions current biomedical challenges.

Language: Английский

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Meta-analysis reveals glucocorticoid levels reflect variation in metabolic rate, not ‘stress’

eLife, Journal Year: 2023, Volume and Issue: 12

Published: June 12, 2023

Glucocorticoid (GC) variation has long been thought to reflect in organismal ‘stress,’ but associations between GCs and Darwinian fitness components are diverse magnitude, direction, highly context-dependent. This paradox reveals our poor understanding of the causes GC variation, contrasting with detailed knowledge functional consequences variation. Amongst an array effects many physiological systems, orchestrate energy availability anticipate recover from predictable unpredictable environmental fluctuations challenges. Although this is mechanistically well-known, extent which levels quantitatively explained by metabolism unresolved. We investigated association through meta-analysis, selecting studies endotherms (1) experiment was performed that affected metabolic rate (2) were measured simultaneously. found increase associated 20 out 21 (32 35 effect sizes). More importantly, there a strong positive correlation increases (p=0.003). pattern similar birds mammals, independent nature experimental treatment. conclude major driver within individuals. Stressors often affect rate, leading us question whether provide information on ‘stress’ beyond stressor’s rate.

Language: Английский

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Modelling the role of glucocorticoid receptor as mediator of endocrine responses to environmental challenge

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1898)

Published: Feb. 5, 2024

Glucocorticoid hormones (GCs) modulate acute 'stress' responses in vertebrates, exerting their actions across many physiological systems to help the organism face and overcome challenges. These take place via binding glucocorticoid receptor (GR), which determines not only magnitude of GC-mediated response but also negative feedback that downregulates GCs restore homeostasis. Although GR function is assumed determine GC regulation capacity, associations between abundance individuals' coping abilities remain cryptic. We developed a dynamic model fitted empirical data predict effects on both plasma patterns response. Individuals with higher GRs showed lower exposure, stronger greater capacity adjust this according stressor intensity, may be translated into more resilient flexible phenotypes. Our results show among-individual variability challenges detectability association measurements responses. approach provides mechanistic insights role function, point at fundamentally driving complex features system environmental change. This article part theme issue 'Endocrine variation: conceptual approaches recent developments'.

Language: Английский

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Integrating theoretical and empirical approaches for a robust understanding of endocrine flexibility

Journal of Experimental Biology, Journal Year: 2022, Volume and Issue: 225(Suppl_1)

Published: March 8, 2022

ABSTRACT There is growing interest in studying hormones beyond single ‘snapshot’ measurements, as recognition that individual variation the endocrine response to environmental change may underlie many rapid, coordinated phenotypic changes. Repeated measures of hormone levels individuals provide additional insight into flexibility – is, how modulate environment. The ability quickly and appropriately modify phenotype predicted be favored by selection, especially unpredictable environments. need for repeated samples from can make empirical studies logistically challenging, but methods based mathematical modeling insights circumvent these challenges. Our Review introduces defines flexibility, reviews existing studies, makes suggestions future work, recommends approaches complement work significantly advance our understanding. Mathematical not yet widely employed endocrinology, used identify innovative areas research generate novel predictions testing.

Language: Английский

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Endocrine flexibility can facilitate or constrain the ability to cope with global change

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1898)

Published: Feb. 5, 2024

Global climate change has increased average environmental temperatures world-wide, simultaneously intensifying temperature variability and extremes. Growing numbers of studies have documented phenological, behavioural morphological responses to in wild populations. As systemic signals, hormones can contribute orchestrating many these phenotypic changes. Yet little is known about whether mechanisms like hormonal flexibility (reversible changes hormone concentrations) facilitate or limit the ability individuals, populations species cope with a changing climate. In this perspective, we discuss different by which flexibility, primarily glucocorticoids, could promote versus hinder evolutionary adaptation regimes. We focus on because it key gradient influenced change, easy quantify, its links are well established. argue that reaction norm connect individual population-level species-wide patterns will be critical for making progress field. also develop case study urban heat islands, where several questions regarding addressed. Understanding allow animals when conditions become more challenging help predicting vulnerable ongoing change. This article part theme issue 'Endocrine variation: conceptual approaches recent developments'.

Language: Английский

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IBRtools: An R package for calculating integrated biomarker indexes

Ecology and Evolution, Journal Year: 2024, Volume and Issue: 14(2)

Published: Feb. 1, 2024

Multibiomarker studies are useful to evaluate the early warning signs of environmental degradation, and their unified responses often assessed through two common indexes, Integrated Biomarker Response (IBR) Biological Responses version 2 (IBRv2). The R package IBRtools allows users calculate both IBR IBRv2 while simultaneously incorporating all biomarkers under evaluation. includes functions for calculating indexes obtaining standardized values, as well a function radar chart creation three example datasets. Here we describe main algorithms involved in calculations, description novel illustrate workflow using data examples available on guide user how accurately acquire values either index or index. provides user-friendly platform obtain making it straightforward even large

Language: Английский

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Covariation between glucocorticoid levels and receptor expression modulates embryo development and postnatal phenotypes in gulls

Hormones and Behavior, Journal Year: 2023, Volume and Issue: 149, P. 105316 - 105316

Published: Jan. 31, 2023

The hypothalamic-pituitary-adrenocortical axis can translate, through glucocorticoid secretion, the prenatal environment to development produce phenotypes that match prevailing environmental conditions. However, whether developmental plasticity is modulated by interaction between circulating glucocorticoids and receptor expression remains unclear. Here, we tested covariation plasma corticosterone (CORT) gene (Nr3c1) in blood underlies embryonic programming yellow-legged gulls (Larus michahellis). We examined variations levels of CORT DNA methylation patterns Nr3c1 response two ecologically relevant factors: adult alarm calls (a cue predator presence) changes light competitive disadvantage). then determined postnatal were associated with expression, explored direct indirect relationships environment, hormone-receptor covariation, phenotypes. Prenatal exposure increased up-regulated gull chicks, while cues reduced both hormone expression. Chicks prenatally exposed showed altered profiles regulatory region, but varied throughout breeding season years. Moreover, our results suggest a negative relationship , at least specific CpG sites. interplay affected embryo timing vocalizations, as well hatchling mass fitness-relevant behaviours. These findings provide link inputs, function phenotypic outcomes, suggesting may underlie free-living animals.

Language: Английский

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Glucocorticoid receptor expression as an integrative measure to assess glucocorticoid plasticity and efficiency in evolutionary endocrinology: A perspective

Hormones and Behavior, Journal Year: 2022, Volume and Issue: 145, P. 105240 - 105240

Published: Aug. 4, 2022

Organisms have to cope with the changes that take place in their environment order keep physical and psychological stability. In vertebrates, hypothalamic-pituitary-adrenal (HPA) axis plays a key role mediating phenotypic adjustments environmental changes, primarily by regulating glucocorticoids (GCs). Although circulating GCs widely been used as proxy for individual health fitness, our understanding of HPA regulation is still very limited, especially free-living animals. Circulating only exert actions when they are bound receptors, therefore, GC receptors play pivotal downstream changes. Because under challenging conditions (as well negative feedback activation) occur mainly through binding low-affinity glucocorticoid (GR), we propose GR activity, particular expression, may crucial dynamics, be ultimately related organismal capacity appropriately respond Thus, suggest expression will provide more comprehensive information variation function. To support this idea, compile previous evidence demonstrating fundamental on responses fine-tuning GCs. We also make predictions about differences responsiveness - associated focusing plasticity efficiency. Finally, discuss current priorities limitations integrating measures into evolutionary endocrinology ecology studies, further research directions towards use study mechanisms activity gather coping strategies stress resilience. Our goals an integrative perspective prompt reconsideration ecological physiological interpretation measurements, motivate tuning dynamic environments.

Language: Английский

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Endocrine responses to environmental variation

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1898)

Published: Feb. 5, 2024

Hormones regulate most physiological functions and life history from embryonic development to reproduction. In addition their roles in growth development, hormones also mediate responses the abiotic, social nutritional environments. Hormone signalling is responsive environmental changes adjust phenotypes prevailing conditions. Both hormone levels receptor densities can change provide a flexible system of regulation. Endocrine flexibility connects environment organismal function, it central understanding impacts effect on individuals populations. may act as 'sensor' link signals epigenetic processes thereby phenotypic plasticity within across generations. Many parameters are now changing unprecedented ways result human activity. The knowledge base organism-environmental interactions was established environments that differ many current conditions ongoing impacts. It an urgent contemporary challenge understand how evolved endocrine will modulate response anthropogenic including climate change, light-at-night chemical pollution. play role ecology, integration into conservation lead more effective outcomes. This article part theme issue 'Endocrine variation: conceptual approaches recent developments'.

Language: Английский

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Do glucocorticoids indicate stress? Meta-analysis reveals a tight association between glucocorticoids and metabolic rate

Published: June 12, 2023

Abstract Glucocorticoid (GC) variation has long been thought to reflect in organismal ‘stress’, but associations between GCs and Darwinian fitness components are diverse magnitude, direction, highly context-dependent. This paradox reveals our poor understanding of the causes GC variation, contrasting with detailed knowledge functional consequences variation. Amongst other things, orchestrate energy availability, anticipate recover from predictable unpredictable environmental fluctuations challenges. Although this is mechanistically well-known, extent which levels quantitatively explained by metabolism unresolved. We investigated association through meta-analysis, selecting studies endotherms (1) an experiment was performed that affected metabolic rate (2) GC-levels were measured simultaneously. found increase associated 20 out 21 (32 35 effect sizes). More importantly, there a strong positive correlation increases (p=0.003). pattern similar birds mammals, independent nature experimental treatment. conclude major driver within individuals. Stressors often affect rate, leading us question whether provide information on ‘stress’ beyond stressor’s rate.

Language: Английский

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