The field of partial reprogramming is moving from successful mouse studies to the first human clinical trials.
The core of this experiment lies in the discovery of Yamanaka factors, proteins specialized in converting adult cells into embryonic stem cells.
Discovery of Yamanaka factors
In a major breakthrough in 2006, Shinya Yamanaka, a stem cell biologist, and his colleagues discovered four transcription factors that possess the ability to reset the adult state to a pluripotent state.
The discovery proved significant because it could pave the way for stem cell-based therapies.
In 2010, biologist Prim Singh and colleague Fred Zacouto proposed a paradigm shift in thinking around anti-aging processes. According to scientists, instead of creating induced pluripotent stem cells, activation of Yamanaka factors could theoretically restore youthfulness while preserving cellular identity.
Later, in 2016, Juan Carlos Izpisúa Belmonte and his team demonstrated the effectiveness of Yamanaka factors in mice. The cyclic expression of these factors extended lifespan because mice with progeria lived longer.
In naturally aged mice, the treatment stimulated the regeneration of damaged muscle and pancreatic tissue. Later studies even showed improved memory performance in older mice.
Partial cellular reprogramming trials in humans
Life Biosciences, a Boston-based biotech company co-founded by Harvard’s David Sinclair, will lead the first human trials for partial cellular reprogramming in 2026.
The trial strategy will focus on the eye and target damage to the nerves in the retina caused by NAION and glaucoma. The mechanism will revolve around delivering three of the four “Yamanaka factors” without c-Myc into the eye via a viral vector.
To ensure safety, the genes are controlled by a genetic switch that is only activated when the patient takes a specific antibiotic.
The first phase will involve approximately 18 participants (12 with glaucoma, 6 with NAION), with a five-year follow-up period to monitor for long-term side effects such as cancer.
“If it works, it will be great. It would be a big step forward,” said Vittorio Sebastiano, a stem cell and reproductive biologist at the University of California, Irvine.
Potential risks
The trials also carry some serious risks. For example, if the scientists push cells too far toward a stem-like state, it can cause uncontrolled cell division, which can lead to a cancer stage.
Cell identity can also be lost during the experiment, as there is a delicate balance between making a cell younger and losing its specific purpose in the body.
Some experts warn that even some trained, reprogrammed cells can behave unpredictably and dangerously.
