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.
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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.
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“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, 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, including atherosclerosis, osteoporosis, and Alzheimer’s disease.
The National Institutes of Health supported the work.
Source: University at Buffalo