Metabolic Overdrive in Elite Sport: A Mechanistic Review on AMPK–mTOR Oscillation, NAD⁺ Economy, and Epigenetic Drift

Elite performance relies on a rhythmic alternation between catabolic and anabolic states orchestrated by AMPK and mTOR. We propose that chronic nutrient or hormonal stimulation can flatten this oscillation and induce a metabolic overdrive state characterized by sustained mTORC1 activation, suppressed autophagy, redox imbalance, and NAD⁺‑dependent silencing of SIRT1 via PARP overactivation, with downstream epigenetic drift. Here we integrate evidence from molecular nutrition, exercise physiology, and cancer biology into a systems framework linking AMPK–mTOR dynamics, the SIRT1–PARP NAD⁺ economy, and chromatin regulation (DNMT/TET, HAT/HDAC, miRNAs). Using elite sport as a natural model of maximal adaptation, we outline mechanistic parallels—not causal equivalence— between performance enhancement and pro‑proliferative signaling. We define testable predictions: (1) prolonged mTORC1 activation (>24 h post‑exercise) associates with ↓AMPK Thr172‑P, ↓NAD⁺ and ↓SIRT1 activity; (2) overreaching with high anabolic load increases PARylation and H3K9ac while reducing TET activity; (3) interventions that periodically restore AMPK (fasted endurance, time‑restricted feeding, polyphenol‑mediated AMPK activation) re‑establish oscillation and reduce redox/epigenetic noise. The Metabolic Overdrive Model provides a mechanistic language for the molecular limits of exercise adaptation and a basis for biomarker‑guided periodization that preserves resilience. No causal inference is claimed.