What are the Yamanaka factors and what do they do?

AgeTech World explores the Yamanaka factors and their relation to healthy ageing.

The Yamanaka factors are a group of protein transcription factors that play a vital role in the creation of induced pluripotent stem cells. 

Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from a somatic cell. 

Stem cells are special cells produced by bone marrow – a spongy tissue found in the centre of some bones – that can turn into different types of blood cells.

In 2006, a study by Drs Kazutoshi and Shinya Yamanaka showed that it was possible to reprogram cells using just four master genes (Yamanaka factors) named Oct4, Sox2, Klf4 and OSKM.

Researchers used the Yamanaka factors to reprogram connective tissue cells back to an embryonic state called pluripotency, a state where the cell behaves like an embryonic stem cell and can become any other cell type in the body.

This discovery paved the way for research into how these Yamanaka factors might be used for cellular rejuvenation and a potential way to combat age-related diseases.

Using the Yamanaka factors may allow researchers to make the clock tick backwards, moving from ageing research to epigenetic rejuvenation research.

Epigenetic rejuvenation reprograms the age of a cell in isolation while maintaining its differentiated state, thus effectively rejuvenating the specialised functions peculiar to that cell type.

Numerous studies have showed how the Yamanaka factors can have a major impact in healthy ageing. 

A 2020 study showed that partial cellular reprogramming improves memory in old mice. As previous studies have shown, partial cellular reprogramming is a balancing act between epigenetically rejuvenating cells and resetting their ageing clocks.

Previous studies have also shown that this balancing act is possible and that by exposing cells just long enough to the reprogramming factors, rejuvenation of the cell is possible without erasing its cellular identity.