PADA Hypothesis V2: The Light-Melatonin-Adenosine-Aging Axis, GRK Receptor Desensitization and Whole-Life Sleep Regulation Model

Abstract

This work presents Version 2 of the PADA Hypothesis, a unified biological framework built upon the light-melatonin-adenosine-aging axis. The hypothesis shifts the traditional "adenosine concentration centrism" paradigm to a "receptor state determinism" model, where sleep pressure and aging outcomes are jointly determined by adenosine ligand concentration and the degree of GRK-mediated adenosine receptor homologous desensitization (D value). This manuscript constructs complete molecular pathways, receptor kinetic functions, and logical closed-loop deduction. It includes an N-of-1 long-term self-observation case with multiple episodes of prolonged wakefulness, which provides real-world observational evidence for the model. Chapter 10 contains natural philosophical speculation and thought experiments, which are distinguished from testable biological hypotheses by an explicit disclaimer. All verifiable biological statements are limited to Chapters 1–9 and require future laboratory validation. The supplementary appendices archive the full iteration history: prior manuscript versions, all deduction records, patch revision logs and original case transcripts, for full open traceability. This preprint is released openly on Zenodo for open scientific discussion, replication and falsification testing.