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A Minimal Model Explains Aging Regimes and Guides Intervention Strategies

Fedichev, P.; Gruber, J.

2025-09-17 systems biology
10.1101/2025.08.25.671954 bioRxiv
Show abstract

Aging varies widely across species yet converges on uni-versal laws such as Gompertzian mortality. We propose a minimal framework that reduces this complexity to three macroscopic variables: the leading stress response (z0), cumulative entropic damage (Z), and regulatory noise strength (D0). The model predicts two regimes. In unstable species such as flies and mice, intrinsic instability drives exponential divergence of biomarkers and mortality. In stable species such as humans, linear damage accumulation steadily erodes the leading stress response, producing a hyperbolic trajectory toward a finite maximum lifespan. The framework reproduces survival curves and methylation dynamics across taxa and organizes intervention strategies into three levels: modulating stress responses, reducing noise, and slowing entropic damage, offering a roadmap for extending human healthspan and lifespan.

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