RT Journal Article SR Electronic T1 Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.08.29.505222 DO 10.1101/2022.08.29.505222 A1 Lucas Schoenfeldt A1 Patrick T. Paine A1 Nibrasul H. Kamaludeen M. A1 Grace B. Phelps A1 Calida Mrabti A1 Kevin Perez A1 Alejandro Ocampo YR 2022 UL http://biorxiv.org/content/early/2022/08/31/2022.08.29.505222.abstract AB The dedifferentiation of somatic cells into a pluripotent state by cellular reprogramming coincides with a reversal of age-associated molecular hallmarks. Although transcription factor induced cellular reprogramming has been shown to ameliorate these aging phenotypes in human cells and extend health and lifespan in mice, translational applications of this approach are still limited. More recently, chemical reprogramming via small molecule cocktails have demonstrated a similar ability to induce pluripotency in vitro, however, its potential impact on aging is unknown. Here, we demonstrated that partial chemical reprogramming is able to improve key drivers of aging including genomic instability and epigenetic alterations in aged human cells. Moreover, we identified an optimized combination of two reprogramming molecules sufficient to induce the amelioration of additional aging phenotypes including cellular senescence and oxidative stress. Importantly, in vivo application of this two-chemical combination significantly extended C. elegans lifespan. Together, these data demonstrate that improvement of key drivers of aging and lifespan extension is possible via chemical induced partial reprogramming, opening a path towards future translational applications.Competing Interest StatementThe authors have declared no competing interest.