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.

CIMUS-USC · biorxiv

Paper

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that genetic and chemical partial reprogramming can ameliorate aging phenotypes by targeting senescent cells without restoring their proliferative capacity. This research addresses the root causes of aging by exploring interventions that directly affect cellular senescence, a key hallmark of aging, thus contributing to the understanding of potential rejuvenation strategies.

Author of this paper? Send a correction.