Comprehensive decoding of aging pathways: hypothesis of metabolic homeostasis cascade collapse convergence and re-drive model(V117))

Abstract Static wear-and-tear theory fails to explain the diversity, non-linear acceleration, and abrupt phenotypic decline of aging. This paper proposes that the essence of aging lies in the cascading collapse and self-locking of metabolic flux homeostasis. Central to this is a core axis model composed of AMPK, mTOR, PGC-1α, and PPARα: the axis shifts from rhythmic oscillation to a non-steady state, converging on a decline in mitochondrial functionality (the first internal driver node). This sequentially triggers disturbances in glucose and lipid metabolism, GH/IGF-1 decline, collapse of antioxidant defenses, inflammation-glucocorticoid hijacking, and accumulation of senescent cells, forming a six-factor self-locking cascade. The theory is strictly defined within the context of human physiology and provides testable predictions (e.g., red blood cell deformability in adolescents as an early marker of axis imbalance), shifting aging interventions from “single-target repair” to “restoring systemic rhythm.” KeywordsAging; mitochondria; metabolic homeostasis; AMPK; mTOR; PGC-1α; PPARα; inflammation; growth hormone; paradigm shift