Researchers Studying Gene With Capacity to Delay, Reverse Aging

Known as Nanog, the gene is the focus of experiments that ignited dormant cell processes key to preventing weak bones, clogged arteries and other telltale signs of growing old.

“Our research into Nanog is helping us to better understand the process of aging and ultimately how to reverse it,” says Stelios Andreadis, PhD, professor of biomedical engineering and the study’s lead author.

Additional authors come from the biomedical engineering department — a joint program between the Jacobs School of Medicine and Biomedical Sciences and UB’s engineering school — and the Department of Biostatistics and Bioinformatics at Roswell Park Comprehensive Cancer Center.

The study, published June 28 in the journal Stem Cells, also show promise in counteracting premature aging disorders such as Hutchinson-Gilford progeria syndrome.

To combat aging, the human body holds a reservoir of nonspecialized cells, called adult stem cells, that can regenerate organs. 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 condition which leads to age-related disorders. Reversing the effects of aging on adult stem cells, essentially rebooting them, can help overcome this problem.

In previous experiments, Andreadis, who is also the professor and chair of the Department of Chemical and Biological Engineering, showed the capacity of adult stem cells to form muscle and generate force declines with aging.

Specifically, he examined a subcategory of muscle cells called smooth muscle cells, which reside in arteries, intestines and other tissues.

In the new study, Panagiotis Mistriotis, a graduate student in Andreadis’ lab and first author, introduced Nanog into aged stem cells.

He found that Nanog opens two key cellular pathways: Rho-associated protein kinase (ROCK) and Transforming growth factor beta (TGF-β).

In turn, this spurs 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.

Andreadis notes 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.

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

The scientists are now focusing on identifying drugs that can mimic the effects of Nanog.

This will allow them to study whether aspects of aging inside the body can also be reversed and could have implications in an array of illnesses from atherosclerosis and osteoporosis to Alzheimer’s disease.

The work was supported by a National Institutes of Health grant awarded to Andreadis.

Co-authors include:

• Ruogang Zhao, PhD, assistant professor of biomedical engineering
• Pedro Lei, PhD, research associate professor of chemical and biological engineering
• Jianmin Wang, PhD, and Song Liu, PhD, of Roswell Park Comprehensive Cancer Center

Other co-authors are, from biomedical engineering, Mohammadnabi Asmani, and, from chemical and biological engineering, Vivek K. Bajpai, PhD; Mao-Shih Liang, PhD; Na Rong, Aref Shahini and Xiaoyan Wang.