The Multi-Counter Architecture of Organismal Aging

The biology of aging is characterized by a proliferation of mechanistic theories—telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis—each supported by compelling data but none sufficient to explain organismal aging in its entirety. This fragmentation hinders the development of predictive models and synergistic interventions. We propose the Multi-Counter Architecture of Organismal Aging (MCAOA), a quantitative, falsifiable framework that models aging as the integrated output of parallel, tissue-specific damage accumulation processes (“counters”). Each counter follows defined kinetics with dimensionally consistent terms for division- and time-driven damage. A core axiom mandates that tissue-specific counter weights be derived, where possible, from biological parameters independent of the aging data used for fitting. By providing a formal, integrative structure, MCAOA aims to offer a mathematical language for operationalizing mechanistic theories into testable models. We conclude with direct experimental tests capable of falsifying its core axioms.