Rewinding the Epigenetic Clock in Human Cells

A study published in Nature Communications reported that aged human cells can be reprogrammed to a youthful state, using a technique that targets errors in the epigenome – the chemical changes to the DNA and its packaging proteins that control gene expression.

Every non-reproductive human cell contains the full human genome, but much of the genome is locked away through epigenetic modifications. DNA can be packaged so as to render it inaccessible, or silenced through a process called methylation. These modifications occur as stem cells differentiate and become committed to a specific function, depending on what tissue they will eventually occupy. It is thought that throughout life, unwanted epigenetic modifications build up, modifying gene expression and leading to age-related pathologies such as cancer and neurodegeneration.

It is possible to erase a cell’s epigenetic modifications, thus reverting it to an embryonic state, by making the cell express nuclear reprogramming factors. This removes any modification errors related to ageing, but also deletes the cell’s identity, causing it to lose it’s specialised function and making this process fatal when applied to whole mice.

However, a 2016 study in mice found that when reprogramming factors were expressed briefly, only age-related epigenetic changes are reversed, resulting in lifespan extension.

This study is the first demonstration that this process can reverse epigenetic ageing in a variety of human cells. Researchers took cartilage cells from patients with osteoarthritis, and found that partial reprogramming could reduce the release of disease-causing inflammatory molecules. Likewise, treatment improved the abilities of aged muscle stem cells to regenerate damaged muscle tissue.

Our results are novel and represent a significant step toward the goal of reversing cellular aging, and have potential therapeutic implications for aging and aging-related diseases.

Sarkar, T., Quarta, M., Mukherjee, S., Colville, A., Paine, P., & Doan, L. et al. (2020). Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells. Nature Communications, 11(1). doi: 10.1038/s41467-020-15174-3