Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful...

Area of Science:

• Evolutionary medicine
• Physiology
• Immunology

Background:

• Chronic inflammatory diseases (CIDs) involve complex maladaptations across multiple physiological systems.
• The underlying reasons for disease sequelae in CIDs remain unclear due to a lack of consideration for energy trade-offs and evolutionary principles.
• Existing research often overlooks the evolutionary context of physiological responses during inflammation.

Purpose of the Study:

• To review the evolutionary basis of physiological supersystems and their role in CIDs.
• To explore the fitness consequences of genes involved in CIDs across different life stages.
• To establish a framework integrating bodily energy regulation and evolutionary medicine for understanding CID pathophysiology.

Main Methods:

• Review of evolutionary medicine principles applied to physiological supersystems.
• Analysis of gene fitness consequences in CIDs considering life-history stages and environmental factors.
• Examination of energy trade-offs during acute inflammatory episodes and their adaptive/maladaptive thresholds.

Main Results:

• Genes positively selected for acute inflammation may lead to maladaptations when inflammation persists.
• Energy regulation is an evolved trait, explaining uniform sequelae across diverse CIDs.
• Specific sequelae include fatigue, metabolic dysfunction, hormonal imbalances, and increased cardiovascular risk.

Conclusions:

• Integrating energy regulation into evolutionary medicine provides a novel framework for understanding CID pathophysiology.
• Evolved energy trade-offs are crucial for comprehending the uniform sequelae observed in various CIDs.
• Future clinical practice should incorporate these evolutionary insights for early diagnosis and symptomatic treatment of CIDs.