Fully deciphering the aging pathway: hypothesis that mitochondrial dysfunction as the primary cause of aging triggers continuous collapse of bodily functions(V106)

Abstract Aging is a complex, multifactorial process that has eluded a unified explanatory framework. Here, we propose a novel integrative hypothesis positioning mitochondrial dysfunction as the primary driver of aging, orchestrating downstream processes across four regulatory axes—metabolic, inflammatory, hormonal, and epigenetic. This “four-axis model” provides a structured representation of 81 potential combinatorial states, capturing the diversity of aging phenotypes observed in humans. Our framework reconciles existing theories of aging, including cellular senescence, chronic inflammation, metabolic dysregulation, and epigenetic drift, by situating them as downstream manifestations of core mitochondrial decline. Importantly, the model suggests that deviations from balanced axis states can act as initiating events, providing mechanistic insight into the heterogeneity of age-related diseases. By integrating empirical evidence with a systems-level perspective, this hypothesis offers testable predictions and a conceptual foundation for targeted interventions aimed at delaying or mitigating aging. Although primarily theoretical, the model is intended to stimulate experimental exploration and foster a more unified understanding of aging biology.