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Energetically constrained turnover drives the emergence of aging

Yao, M.; Deguchi, S.

2026-05-21 biophysics
10.64898/2026.05.19.726278 bioRxiv
Show abstract

Aging is characterized by progressive functional decline, yet why such decline is observed broadly across living systems remains unclear. While molecular and cellular mechanisms describe how aging progresses, they do not explain why functional decline should arise as a natural consequence of living organization. Here, we show that aging naturally emerges from three general features of life: unavoidable damage, turnover-mediated maintenance, and the energetic constraint of turnover. We develop a hierarchical damage-turnover model in which component-level damage and energetically constrained turnover jointly determine whole-system performance. In the model, damage stochastically converts functional components into non-functional components, whereas turnover restores component performance at a rate coupled to whole-system performance. Analytical and Monte Carlo analyses reveal two regimes: a non-aging regime, in which performance remains finite, and an aging regime, in which performance progressively collapses toward zero. Performance-independent turnover always maintains a positive steady state, whereas performance-dependent turnover generates irreversible decline when reduced performance weakens maintenance capacity. Stochastic fluctuations further promote collapse near the transition boundary, even when deterministic analysis predicts a nonzero steady state. These results indicate that unavoidable damage and energetically constrained turnover are sufficient to generate aging-like decline, providing a minimal theoretical explanation for long-term irreversibility in biological systems.

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