The Essence of Nature Can be the Simplest (6)–Lifespan: Determined by Extracellular Fenton Chemistry

Understanding the determinants of lifespan is a central objective in biology. Lifespan is shaped by dynamic, stage-specific changes in metabolism, energy allocation, and genome integrity. Heart rate serves as a physiological marker that reflects both life stage and metabolic state. Recent studies suggest that all cells perform extracellular Fenton chemistry for holistic energy to power the heartbeat and maintain body temperature, and nucleotides are a source of the reaction substrates in this process. This article synthesizes current evidence on the dynamic changes in heart rate, metabolic rate, and metabolic pathways across key developmental and aging stages. We propose that human lifecycle can be conceptualized as a progressive decline in extracellular Fenton chemistry: beginning with the rapid fetal heartbeat driven by glycolysis-mediated extracellular Fenton activity, transitioning through a developmental shift toward increased intracellular ATP production and declining heart rate, and culminating in the cessation of cardiac activity during aging. The Fenton reactions mediated by DNA in cells lead to mitochondrial formation as a thermochemical restructuring product, analogue to charcoal production. Hutchinson-Gilford progeria syndrome (HGPS) represents an extreme case of persistently elevated extracellular Fenton chemistry. This study highlights the energetic and chemical mechanisms underlying the unifying theme of irreversible properties of life.