Student Scintillon Institute San Diego, California, United States
Abstract: Aging is a natural process that significantly impacts global health, vitality, and quality of life for people. Here, we report several exciting recent advances in the field of partial cell reprogramming, a potential anti-aging approach that rejuvenates cells without converting cellular identity as in reprogramming. We have developed a novel mRNA-based method that utilizes a cocktail of 6 mRNA-coded reprogramming factors and an in vitro treatment regimen that robustly and reproducibly improves well-known cellular biometrics in a stepwise fashion.
Using human skin-derived fibroblasts as a model for aged cells, we demonstrate that our 6F-mRNA method significantly improved numerous cell parameters, notably elongation of telomeres, activated cell cycle, increased cell proliferation, and partially rescued cell cycle arrest when compared to control. Moreover, other positive alterations included enhanced mitochondrial membrane potential and partially reversed age-related declines in mitophagy. Epigenetically, the cellular profiles appeared to be consistent with a more rejuvenated state. Finally, using embryonic-specific feature testing, we demonstrated that nestin expression, cell growth clustering, and cell movement using a scratch assay appeared to be enhanced.
Overall, these findings reinforce and add to current evidence suggesting that mRNA-directed cell rejuvenation is feasible. Studies on an extensive panel of human iPSC-derived cells are currently underway in research and cGMP settings that can be used to support future preclinical and clinical studies.
