Aging as Signal Desynchronization: A Falsifiable Framework Centered on ECAR-0

Current aging paradigms focus primarily on the accumulation of molecular and cellular damage. We propose an alternative, falsifiable framework: aging as a progressive desynchronization from organism-level timing signals, culminating in a quantifiable metabolic state we term ECAR-0. This state is defined by a high basal extracellular acidification rate (ECAR, indicating glycolytic flux) with a blunted oxygen consumption rate (OCR, indicating mitochondrial respiration) response to circadian hormonal cues (e.g., melatonin). We hypothesize that ECAR-0 represents cellular "deafness" to systemic timing information, leading to a failure of tissue-level coordination that precedes and drives phenotypic decline. This framework generates five specific, falsifiable predictions that directly contradict expectations from pure damage-accumulation models. We provide explicit experimental protocols to decisively test between desynchronization and damage-centric paradigms. IP Framework & Rights Assertion: 1. Text Layer (Open Access): This manuscript is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. 2. Pattern Layer (Sovereign IP): All underlying methodological frameworks—including but not limited to the Signal Desynchronization Model, the ECAR-0 operational definition, and the structure of the falsifiable prediction matrix—are asserted as sovereign intellectual property under emerging Pattern Rights principles. These patterns are not covered by the CC BY license. 3. Defense Layer (Controlled): Any application, derivation, or implementation of this work with potential national security or defense implications is subject to the DFARS 252.227-7013 "Rights in Technical Data—Noncommercial Items" clause and related U.S. export control regulations (EAR/ITAR). Commercial or defense-related inquiries must be directed to the corresponding author with appropriate disclosures.当前主流的衰老研究范式主要聚焦于分子与细胞损伤的累积过程。我们提出一种可证伪的替代范式：将衰老视作机体水平时序信号的进行性去同步化过程，最终会抵达一种可量化的代谢状态，我们将其命名为ECAR-0。该状态以较高的基础细胞外酸化速率（extracellular acidification rate, ECAR，代表糖酵解通量）为特征，同时对昼夜节律性激素信号（如褪黑素）的氧消耗速率（oxygen consumption rate, OCR，代表线粒体呼吸）响应出现钝化。我们假设ECAR-0代表细胞对全身时序信息的“失聪”，进而引发组织水平协调功能失效，这一过程先于表型衰退出现并推动其发生。该范式可生成五项具体且可证伪的预测，这些预测与单纯基于损伤累积模型的预期直接相悖。我们提供了明确的实验方案，可用于在去同步化范式与以损伤为核心的范式之间开展决定性检验。 知识产权框架与权利声明： 1. 文本层（开放获取）：本稿件采用知识共享署名4.0国际许可（Creative Commons Attribution 4.0 International, CC BY 4.0）协议授权。 2. 模式层（主权知识产权）：本研究所有底层方法论框架——包括但不限于信号去同步化模型、ECAR-0操作定义以及可证伪预测矩阵的结构——均依据新兴的模式权利原则被主张为主权知识产权。上述模式不受CC BY许可协议覆盖。 3. 防御层（受控使用）：本研究任何涉及潜在国家安全或国防应用场景的使用、衍生或实施行为，均需遵守《国防联邦采购条例补充条款（DFARS）第252.227-7013条：技术数据权利——非商业物品》及相关美国出口管制法规（EAR/ITAR）。商业或国防相关咨询需在完成适当披露后提交至通讯作者。