OSK Partial Reprogramming Under Chronic Infection

Linked theories: Pathogen Control (Lidsky), Epigenetic Information (Sinclair)

Hypothesis

Partial reprogramming improves healthspan; under chronic infection, it incurs infection tradeoffs unless pathogen control co-improves.

Design

• Model: Aged C57BL/6J (20 months).
• Infection: Chronic low-virulence pathogen model (ABSL-2).
• Arms (N=40/arm): Vehicle; OSK regimen; Antiviral/Vaccine; OSK+Antiviral.
• Dosing: OSK weekly cycles (1w on/2w off) per tolerability pilot; doxycycline-controlled.

Endpoints

• Hazard, maximum lifespan, infection burden, tumor incidence, epigenetic age.

Time & Cost (est.)

• 12–18 months; $450k–$900k.

Discriminator

• PC: OSK alone shows infection penalty or limited hazard gain vs combined arm.
• Sinclair: OSK extends lifespan without infection penalty under challenge.