The Bio-Energetic
Sequencing Model

The first priority in any rejuvenation protocol must be rebuilding cellular energy capacity. NAD+ serves as both an electron carrier in cellular respiration and a substrate for sirtuins and PARPs—enzymes critical to DNA repair and metabolic regulation.

Phase 1 focuses exclusively on NAD+ restoration through NMN or NR supplementation, supported by substrate availability optimization (B vitamins, methyl donors). No other interventions are introduced during this phase.

With energy capacity restored, the cell can now fund housekeeping processes. Phase 2 introduces pulsed mTOR inhibition via rapamycin to stimulate autophagy—the clearance of misfolded proteins, damaged mitochondria, and accumulated debris.

The pulsing protocol is critical. Chronic mTOR inhibition suppresses protein synthesis and immune function. Pulsed dosing (weekly administration) provides autophagy stimulus while allowing recovery between doses.

Only after energy restoration and autophagy-mediated cleanup can senolytic therapy succeed. Senolytics kill senescent cells—but killing is only half the problem. The debris from dying senescent cells must be cleared by neighboring tissue.

If neighbors lack energy reserves or have impaired autophagy, senolytic therapy generates inflammatory overload rather than rejuvenation. Phase 3 introduces senolytic compounds to energy-replete tissue with active autophagy.

With senescent cells cleared and tissue prepared, Phase 4 introduces stem cell support interventions. The cleared terrain allows stem cells to function without interference from senescent cell signaling.

This phase may include exogenous stem cell therapy or interventions that activate endogenous stem cell populations. The specific approach depends on target tissues and individual response to earlier phases.

The final phase focuses on maintaining the rejuvenated cellular state through epigenetic interventions. This may include partial cellular reprogramming through transient Yamanaka factor expression.

Phase 5 represents the frontier of longevity intervention. Current research explores methods to reset epigenetic age while maintaining cellular identity and function.