neuron-specific expression of reprogramming factor orthologs does not alleviate age-related cognitive decline.

Overexpression of the OSK(M) (Oct4, Sox2, Klf4, with or without cMyc) pluripotency factors have shown promise in rejuvenating the function of aged neurons. To test whether this intervention could also ameliorate age-associated cognitive decline, we used a doxycycline inducible system to overexpress the OSK orthologs specifically in aging neurons. We find that OSK does not improve short-term associative memory or extend lifespan and can further disrupt chemotaxis behavior. Taken together, our data suggest that OSK-mediated partial reprogramming may have deleterious effects on post-mitotic neurons that function in cognitive processes.