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Can a stem cell gene called Nanog reverse aging? - Futurity

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In a series of experiments, an embryonic stem cell gene kicked into action dormant cellular processes that are key to preventing weak bones, clogged arteries, and other telltale signs of growing old.

The gene, called Nanog, also shows 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, professor and chair of the chemical and biological engineering department at the University at Buffalo School of Engineering and Applied Sciences.

To battle aging, the human body holds a reservoir of nonspecialized cells that can regenerate organs. These cells, called adult stem cells, 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, scientists say.

Andreadis has previously shown that 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.

Panagiotis Mistriotis, a graduate student in Andreadis’ lab and first author of the study in the journal Stem Cells, introduced Nanog into aged stem cells. The findings show 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, noting that 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.


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Study Shows How the Nanog Protein Promotes Growth of Head and Neck Cancer

A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James) has identified a biochemical pathway in cancer stem cells that is essential for promoting head and neck cancer.

The study shows that a protein called Nanog, which is normally active in embryonic stem cells, promotes the growth of cancer stem cells in head and neck cancer. The findings provide information essential for designing novel targeted drugs that might improve the treatment of head and neck cancer.

Normally, Nanog helps healthy embryonic stem cells maintain their undifferentiated, uncommitted (i.e., pluripotent) state. But recent evidence suggests that Nanog promotes tumor growth by stimulating the proliferation of cancer stem cells.

“This study defines a signaling axis that is essential for head and neck cancer progression, and our findings show that this axis may be disrupted at three key steps,” says principal investigator Quintin Pan, PhD, associate professor of otolaryngology at the OSUCCC – James. “Targeted drugs that are designed to inhibit any or all of these three steps might greatly improve the treatment of head and neck cancer.”

The findings were published in a recent issue of the journal Oncogene.

Specifically, the study shows that an enzyme called “protein kinase C-epsilon” (PKCepsilon) adds energy-packing phosphate groups to the Nanog molecule. This phosphorylation of Nanog stabilizes and activates the molecule.

It also triggers a series of events: Two Nanog molecules bind together, and these are joined by a third “co-activating” molecule called p300. This molecular complex then binds to the promoter region of a gene called Bmi1, an event that increases the expression of the gene. This, in turn, stimulates proliferation of cancer stem cells.

“Our work shows that the PKCepsilon/Nanog/Bmi1 signaling axis is essential to promote head and neck cancer,” Pan says. “And it provides initial evidence that the development of inhibitors that block critical points in this axis might yield a potent collection of targeted anti-cancer therapeutics that could be valuable for the treatment of head and neck cancer.”

(Image: Gray’s Anatomy of the Human Body)

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medicalxpress.com
Embryonic gene Nanog reverses aging in adult stem cells
The fountain of youth may reside in an embryonic stem cell gene named Nanog.

The fountain of youth may reside in an embryonic stem cell gene named Nanog.

In a series of experiments at the University at Buffalo, 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, published June 29 in the journal Stem Cells, 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, professor and chair of the Department of Chemical and Biological Engineering at the UB School of Engineering and Applied Sciences, and the study’s lead author.

Additional authors come from UB’s Department of Biomedical Engineering, a joint program between UB’s engineering school and the Jacobs School of Medicine and Biomedical Sciences at UB, and the Department of Biostatistics and Bioinformatics at Roswell Park Cancer Institute in Buffalo.

To battle aging, the human body holds a reservoir of nonspecialized cells that can regenerate organs. These cells are calledadult 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.

Andreadis previously showed that 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 of the study, 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 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, noting that 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 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.

Explore further: Why do aged muscles heal slowly?

More information: Panagiotis Mistriotis et al, NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression, STEM CELLS (2016). DOI: 10.1002/stem.2452

Journal reference: Stem Cells

Provided by: University at Buffalo