SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING

Nunez-Quintela, V.; Chantrel, J.; Prados, M. A.; Pedrosa, P.; Lorandi, I.; Lorenzo Rodriguez, L.; Chen, C.; Paredes, R.; Failde-Fiestras, A.; Gonzalez-Perez, D.; Miralles, A.; Da Silva-Alvarez, S.; Lobato-Busto, R.; Gonzalez-Barcia, M.; Alcon, C.; Montero, J.; Marques, P.; Chondronasiou, D.; Pietrocola, F.; Serrano, M.; Kovatcheva, M.; Gomez-Duran, A.; Li, H.; Collado, M.

doi:10.64898/2026.01.13.699211

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bioRxiv · 10.64898/2026.01.13.699211

SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING

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Abstract

Partial reprogramming has emerged as a promising strategy to ameliorate aging phenotypes, yet its cellular targets and mechanisms remain poorly defined. Cellular senescence is a central hallmark of aging and a plausible mediator of reprogramming-induced rejuvenation. Here we show that genetic and chemical partial reprogramming act directly on senescent cells without restoring proliferative capacity. OSKM expression or a reduced two-compound regimen, tranylcypromine and RepSox (2c), attenuates senescence-associated secretory activity, restores mitochondrial homeostasis and apoptotic priming, and improves functional and inflammatory parameters in aged mice, establishing senomorphic, identity-preserving reprogramming as a potentially safer aging intervention.

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Nunez-Quintela, V., Chantrel, J., Prados, M. A., Pedrosa, P., Lorandi, I., Lorenzo Rodriguez, L., Chen, C., Paredes, R., Failde-Fiestras, A., Gonzalez-Perez, D., Miralles, A., Da Silva-Alvarez, S., Lobato-Busto, R., Gonzalez-Barcia, M., Alcon, C., Montero, J., Marques, P., Chondronasiou, D., Pietrocola, F., Serrano, M., Kovatcheva, M., Gomez-Duran, A., Li, H., Collado, M.. 2026-01-13. SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING. https://doi.org/10.64898/2026.01.13.699211

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