Aging as the wound that fails to heal: a bioenergetic continuum of resolution failure.

Abstract

Aging may be conceptualized as a wound that fails to heal, characterized by persistent, unresolved inflammation. Building on Ogrodnik's "unhealed wound" model, this Perspective extends the Exposure-Related Malnutrition (ERM) framework to propose a bioenergetic interpretation of aging. ERM links chronic stress adaptation, nutrient misallocation, and mitochondrial insufficiency to sustained bioenergetic debt that impedes the transition from catabolic containment to anabolic repair. Across tissues, this energetic shortfall manifests as metabolic inflexibility, lipid-droplet accumulation, and a continuum of adaptive mitochondrial dysfunction that remains reversible until the threshold of senescence-the terminal stage of unresolved adaptation. Recognizing bioenergetic availability as the principal determinant of regenerative success reframes mitochondrial dysfunction and senescence not as primary causes of aging but as downstream consequences of chronic energetic exhaustion. Within this continuum, aging reflects a progressive loss of rhythmic catabolic-anabolic cycling that supports metabolic adaptation. Transient metabolic stress normally induces hormetic activation followed by anabolic recovery, but when this oscillation fails, adaptive hormesis gives way to maladaptive exhaustion. Aging thus emerges from the erosion of bioenergetic rhythm-a transition from recovery with renewal to endurance without repair.