The biological state hypothesis: biological state as a systems-level constraint on human adaptive capacity

Area of Science:

• Systems Physiology
• Integrative Biology
• Biomedical Research

Background:

• Current biomedical approaches often use a reductionist model, focusing on individual systems or biomarkers.
• This fragmented view struggles to explain complex phenomena like chronic disease, accelerated aging, and varied individual responses to environmental stressors.
• A holistic framework is needed to understand the organism's integrated physiological condition and adaptive trajectories.

Purpose of the Study:

• To propose the biological state hypothesis (BSH) as a theoretical framework in systems physiology.
• To define biological state as an emergent property of integrated physiological layers: systemic regulation, metabolism, and biological plasticity.
• To reframe chronic disease and aging as downstream consequences of a deteriorating biological state and narrowed adaptive capacity.

Main Methods:

• The BSH integrates three interdependent layers: systemic regulation (autonomic, neuroendocrine, immune-inflammatory, circadian axes), metabolism (energy generation, allocation, utilization), and biological plasticity (neuroplasticity, epigenetic-genomic plasticity).
• It posits that environmental influences impact biological plasticity primarily through systemic regulation and metabolism.
• Adaptive capacity is presented as an emergent property of the coherence among these three layers.

Main Results:

• The BSH posits that a coherent interaction among systemic regulation, metabolism, and plasticity leads to broad adaptive reserve.
• Conversely, persistent dysregulation across these domains progressively narrows adaptive capacity.
• Chronic diseases and accelerated aging are viewed as late-stage manifestations of this sustained deterioration in biological state.

Conclusions:

• The biological state hypothesis (BSH) provides a unified framework for understanding human health and disease.
• It emphasizes the importance of integrated physiological function and adaptive capacity across the lifespan.
• The BSH generates testable predictions and offers a foundation for developing interventions to restore adaptive capacity.