Embryonic gene Nanog reverses aging in adult stem cells

The fountain of youth may reside in an embryonic stem cell gene named Nanog. In a series of experiments, the gene kicked into action dormant cellular processes that are key to preventing weak bones, clogged arteries and other telltale signs of growing old. The findings also show promise in counteracting premature aging disorders such as Hutchinson-Gilford progeria syndrome.

“Our research into Nanog is helping us to better understand the process of aging and ultimately how to reverse it,” says Stelios T. Andreadis, PhD, the study’s lead author.

To battle aging, the human body holds a reservoir of non-specialized cells that can regenerate organs. These cells are called adult stem cells, and they are located in every tissue of the body and respond rapidly when there is a need.

But as people age, fewer adult stem cells perform their job well, a scenario which leads to age-related disorders. Reversing the effects of aging on adult stem cells, essentially rebooting them, can help overcome this problem.

The team previously showed that the capacity of adult stem cells to form muscle and generate force declines with aging. Specifically, they examined a subcategory of muscle cells called smooth muscle cells which reside in arteries, intestines and other tissues.

In the new study, the group introduced Nanog into aged stem cells. They found that Nanog opens two key cellular pathways: Rho-associated protein kinase (ROCK) and Transforming growth factor beta (TGF-β).

In turn, this jumpstarts dormant proteins (actin) into building cytoskeletons that adult stem cells need to form muscle cells that contract. Force generated by these cells ultimately helps restore the regenerative properties that adult stem cells lose due to aging.

“Not only does Nanog have the capacity to delay aging, it has the potential in some cases to reverse it,” says Andreadis.

The embryonic stem cell gene worked in three different models of aging: cells isolated from aged donors, cells aged in culture, and cells isolated from patients with Hutchinson-Gilford progeria syndrome.

The images above show, from left to right, functioning stem cells, stem cells no longer functioning due to Hutchinson-Gilford Progeria syndrome (HGPS), and stem cells previously not functioning due to HGPS that were rebooted by the embryonic stem cell gene Nanog.
Image credit goes to: Stelios Andreadis

Additionally, the researchers showed that Nanog activated the central regulator of muscle formation, serum response factor (SRF), suggesting that the same results may be applicable for skeletal, cardiac and other muscle types.

The researchers are now focusing on identifying drugs that can replace or mimic the effects of NANOG. This will allow them to study whether aspects of aging inside the body can also be reversed. This could have implications in an array of illnesses, everything from atherosclerosis and osteoporosis to Alzheimer’s disease.

Sources:
Mistriotis, P., Bajpai, V., Wang, X., Rong, N., Shahini, A., Asmani, M., Liang, M., Wang, J., Lei, P., Liu, S., Zhao, R., & Andreadis, S. (2016). NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression STEM CELLS DOI: 10.1002/stem.2452