Can aging be reversed? First human trials set to begin

The field of partial reprogramming is transitioning from successful mouse studies to its first human clinical trials.

At the heart of this experiment lies the discovery of Yamanaka factors, proteins specialized in turning adult cells back into embryonic-like stem cells.

Discovery of Yamanaka factors

In 2006, Shinya Yamanaka, a stem-cell biologist, and his colleagues discovered four transcription factors in a major breakthrough, possessing the ability to reset adult state to a pluripotent state.

The discovery proved significant as it could pave the way to stem-cell based therapies.

In 2010, biologist Prim Singh and colleague Fred Zacouto proposed a paradigm shift in thinking surrounding anti-aging processes. According to scientists, instead of creating induced pluripotent stem cells, the activation of Yamanaka factors could theoretically restore youthfulness while maintaining 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 as mice with progeria lived longer.

In naturally aged mice, the treatment boosted the regeneration of damaged muscle and pancreatic tissue. Subsequent studies even indicated improved memory performance in elderly mice.

Partial cellular reprogramming trials in humans

A Boston-based biotech firm co-founded by Harvard’s David Sinclair, Life Biosciences is set to lead the first human trials for partial cellular reprogramming in 2026. 

The trial strategy will focus on the eye, targeting retinal nerve damage caused by NAION and glaucoma. The mechanism will revolve around delivering three of the four “Yamanaka factors” without c-Myc into the eye through a viral vector.

To ensure safety, the genes are governed by a genetic switch that only activates when the patient takes a specific antibiotic.

The initial 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 like cancer.

“If it works, it will be a blast. It would be a great step forward,” said Vittorio Sebastiano, a stem-cell and reproductive biologist at the University of California, Irvine.

Potential risks

The trials also pose some serious risks. For instance, if the scientists push cells too far toward a stem-like state, it can trigger uncontrolled cell division, leading to cancerous stage.

During the experiment, cell identity can also be lost as there is a delicate balance between making a cell younger and causing it to lose its specific purpose in the body.

Some experts warn that even some trained reprogrammed cells could also act unpredictably and dangerously.