Scientists at the Babraham Institute in the United Kingdom, led by Diljeet Gill and Wolf Reik, published a groundbreaking study in the journal eLife that could change the way we understand aging. The research, titled “Multi-omic rejuvenation of human cells by maturation phase transient reprogramming” (Gill et al., 2022), presents a technique called MPTR (Maturation Phase Transient Reprogramming), which rejuvenates human cells without completely losing their original identity.
The study used dermal fibroblasts from middle-aged donors, temporarily reprogramming them with Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) until the maturation phase, before stopping the process. The results are impressive: the transcriptome was rejuvenated by approximately 30 years, while the epigenome, including H3K9me3 levels and the DNA methylation clock, also showed a significant reversal. Furthermore, the cells produced youthful levels of collagen and showed partial improvements in migration speed, suggesting functional benefits.
Dr. Elodia Ávila, a physician specializing in longevity and a researcher, commented on the impact of this discovery: “This study is a milestone in the science of rejuvenation. The MPTR technique demonstrates that we can reverse aspects of cellular aging, such as epigenetic and transcriptomic changes, without compromising cell identity. This opens the door to regenerative therapies that can treat not only skin but also neurodegenerative diseases and arthritis, offering a future where the body not only looks younger, but actually is younger, cell by cell.”
The research highlights that, unlike complete reprogramming for induced pluripotent stem cells (iPSCs), which erases cellular identity, MPTR allows cells to return to their original state after rejuvenation. This was evidenced by analyses of morphology, DNA methylation, and gene expression, which showed that the rejuvenated fibroblasts maintained typical characteristics, such as the expression of the FSP1 marker.
Dr. Ávila added: “What makes this method promising is the substantial reversal of approximately 30 years in the cells’ biological clock, something far superior to previous transient reprogramming approaches, which achieved only approximately 3 years. This suggests that there are optimal time windows to maximize benefits, which may guide future therapies.”
The authors suggest that epigenetic memory and the persistence of some fibroblast genes, such as those related to collagen organization, may be responsible for the cells’ ability to regain their identity. The technique also indicates potential for clinical applications, such as the treatment of age-related diseases, although further studies are needed to validate its safety and efficacy in humans.
For Dr. Ávila, the future is hopeful: “Imagine therapies that regenerate tissue and combat diseases like Alzheimer’s and cataracts. This study gives us a solid foundation to explore these possibilities, and I’m optimistic about what lies ahead.”
The full study is available in the Gene Expression Omnibus repository (accession GSE165180), and the results were published in 2022, marking a significant step toward more accessible regenerative medicine.
