Partial Cellular Reprogramming: Epigenetic Age Reset vs. Teratoma Risk

Reprogramming Protocol

OSKM dose 40%

Baseline aging drift 35%

Senolytic clearance rate 20%

Tissue State

Mean age

0.0

Senescent

0.0%

Identity loss

0.0%

Tissue fitness100%

How it works

Every cell in this tissue block carries an epigenetic age index a ∈ [0,100] (a stand-in for a real DNA-methylation clock) and an identity index d ∈ [0,100] tracking how far it has drifted from its differentiated state toward a pluripotent-like one:

da/dt = drift · (1 + 1.5 · S_local)  −  dose · R(t)
dd/dt = +dose · R(t) · k_id   (reprogramming active)
dd/dt = −k_redif             (reprogramming off, if not locked)

where S_local is the fraction of a cell's lattice neighbours that are senescent, and R(t) is 1 during an active OSKM pulse or in continuous mode, 0 otherwise.

OSKM dose — strength of Oct4/Sox2/Klf4/c-Myc reprogramming factors: it lowers epigenetic age but simultaneously pushes the identity index up.
Pulse OSKM — a short, time-limited reprogramming window (the cyclic protocol used in mouse-lifespan studies): after the pulse ends, identity relaxes back down if it never crossed the loss threshold.
Continuous — sustained reprogramming with no recovery window; identity keeps climbing until cells lock into identity loss (magenta) — the in-vivo teratoma-risk regime seen when OSKM is left on too long.
Senescence (a ≥ 70) — a cell turns grey and starts a paracrine SASP signal that raises its neighbours' drift rate — senescence spreading bystander-style through the tissue.
Senolytic clearance — removes senescent and identity-locked cells, replacing them with a fresh young cell (a = 0, d = 0), mirroring drugs like dasatinib+quercetin.

Real-world grounding: partial in-vivo OSKM reprogramming reversed vision loss and epigenetic age markers in mice (Lu et al. 2020, Sinclair lab); sustained reprogramming instead produced teratomas (Abad et al. 2013, Ohnishi et al. 2014) — the trade-off this simulation makes tunable.

Young cell Old cell Senescent (SASP) Identity loss

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