The energy resistance principle

Living organisms are physical-energetic systems that must obey simple principles guiding energy transformation across physical and temporal scales. The energy resistance principle (ERP) describes behavior and transformation of energy in the carbon-based circuitry of biology. We show how energy resistance (éR) is the fundamental property that enables transformation, converting into useful work the unformed energy potential of food-derived electrons fluxing toward oxygen. Although éR is required to sustain life, excess éR directly causes reductive and oxidative stress, heat, inflammation, molecular damage, and information loss-all hallmarks of disease and aging. We discuss how disease-causing stressors elevate éR and circulating growth differentiation factor 15 (GDF15) levels, whereas sleep, physical activity, and restorative interventions that promote healing minimize éR. The ERP is a testable general framework for discovering the modifiable bioenergetic forces that shape development, aging, and the dynamic health-disease continuum.