A Conceptual Framework of Bioenergetic Trade-Offs in Stress Adaptation, Aging, and Chronic Disease

While global lifespan continues to rise, healthspan—the period of life spent in good health—remains stagnant or in decline. This widening gap reflects more than chronic disease burden; it signals the hidden metabolic cost of prolonged stress adaptation. Under sustained physiological strain, the body reallocates energy and nutrients away from maintenance and repair toward short-term survival priorities such as immune defense and glucose mobilization. Although initially protective, these trade-offs progressively impair recovery, erode resilience, and accelerate biological aging. Current stress and aging frameworks, including allostatic load, describe cumulative burden but lack the resolution to detect early, reversible stages of metabolic compromise—especially in individuals without weight loss or intake deficiency. To address this, we propose Exposure-Related Malnutrition (ERM): a subclinical condition marked by chronic substrate misallocation under stress, despite adequate caloric intake or BMI. ERM represents an early inflection point of adaptive failure with implications for aging, resilience, and chronic disease. This thematic narrative review integrates findings from endocrinology, immunometabolism, mitochondrial biology, and systems physiology. We present a unifying three-phase model of stress response—Respond → Adapt → Resolve—and show how bioenergetic constraints during the resolution phase shape divergent outcomes: homeostasis, hormesis, or maladaptation. Clinically, ERM reframes unexplained fatigue, anabolic resistance, or immune dysfunction as signs of early metabolic imbalance. Recognizing ERM enables earlier detection and supports biomarker-guided, resilience-informed interventions aimed at preserving healthspan by addressing the energetic cost of unresolved adaptation.