What changes inside the cell?
Cells share much of the same DNA but use it differently. A nerve cell and a skin cell maintain different patterns of gene activity. The epigenome helps organise those patterns through DNA methylation, histone modifications and the structure of chromatin.
Reprogramming factors can change that regulatory state. Researchers often study combinations derived from OCT4, SOX2, KLF4 and c-MYC, known as the Yamanaka factors. The choice of factors, their level of activity and the duration of exposure all matter. Partial reprogramming limits the intervention rather than taking cells all the way to pluripotency.
Preserving identity is an objective that experiments must measure. Some protocols temporarily disrupt aspects of identity before cells recover them. A younger molecular profile and a functioning specialised cell are distinct outcomes.
What does the evidence show?
Human cells in culture
Gill and colleagues studied transient reprogramming in human fibroblasts. Their 2022 paper reported younger profiles in measures of DNA methylation and gene expression, alongside changes in collagen production and cell migration. The cells temporarily lost and then recovered fibroblast identity. This was research in cultured cells. Read the eLife study.
Retinal function in mice
Lu and colleagues used OCT4, SOX2 and KLF4, or OSK, in mouse retinal ganglion cells. Their 2020 study connected reprogramming with axon regeneration and improvements in visual function in the experimental settings studied. It provides a way to examine molecular change alongside a tissue’s function. Read the Nature study.
These experiments support further development. The route to a human therapy requires evidence about delivery, control, safety, durability and benefit in the intended tissue and patient population.
How do we measure progress?
Epigenetic clocks estimate biological age from molecular patterns. They are useful research tools, but a change in a clock does not by itself establish improved health. Research also needs to examine cell identity, tissue function, unwanted growth, immune responses and how long an effect lasts.
Delivery is equally important: which cells receive the intervention, how much activity they experience and whether it can be stopped. These practical questions shape the development of reprogramming and gene therapies.
199 Biotechnologies and Boris Djordjevic
199 Biotechnologies was founded by Boris Djordjevic to advance partial reprogramming and longevity biotechnology. Our current direction is human application and wider access to reprogramming and gene therapies. Our next programmes are being developed in stealth.
Boris’s published work includes co-authorship of the 2024 review Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity. The ARDD 2024 programme also lists his talk, “Translating to clinics”. These contributions connect our company’s work with the wider aging research community.
We work closely with Triple Helix and Dr. Patrick Sewell as we pursue this next chapter. Contact us about research collaboration.
Sources and further reading
- Multi-omic rejuvenation of human cells by maturation phase transient reprogrammingGill et al. · eLife · 2022
- Reprogramming to recover youthful epigenetic information and restore visionLu et al. · Nature · 2020
- Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevityLyu et al. · Aging · 2024 · Boris Djordjevic, co-author