Can epigenetic reprogramming reverse ageing?

Epigenetic reprogramming is producing impressive results in animal research. In mice, temporary activation of three proteins (known as OSK, a combination of three growth factors) restored ageing patterns in retinal cells. Mice with glaucoma or age-related vision loss partially regained their sight, and damaged nerve fibres regrew. In another mouse model, brief activation of four of these factors (OSKM) extended lifespan in cases of premature ageing and improved muscle recovery in ordinarily aged mice.

At the cellular level, results have also been obtained using human material. Six different chemical cocktails were able to make human cells in the laboratory 'younger' within a week at the level of gene activity, without the cells losing their identity. Analysis of gene expression data from more than forty human tissue types showed that cells gradually lose their specific characteristics as they age. Partial reprogramming was able to reverse this pattern in cell models. A specific small molecule that removes epigenetic blockades additionally promoted myelin repair in animal models and in laboratory models based on human stem cells, which is of interest for diseases such as multiple sclerosis.

However, these results have not yet been demonstrated in actual humans. No clinical trials for reprogramming have been published in the available literature. Cell and animal research does not by any means always translate to humans, and that makes it too early for firm statements about practical application.

The safety risk deserves explicit attention. If reprogramming goes too far or lasts too long, cells can completely lose their tissue identity and go off course towards tumour formation. 'Partial' reprogramming is specifically designed to limit this risk by keeping activation temporary and brief, but the safety window in humans is still entirely unknown. This is not a hypothetical objection: it is one of the central challenges in the field.