Nanog Gene Reverses Aging in Adult Stem Cells

Professor Stelios Andreadis from SUNY Buffalo and his colleagues have, in a series of elegant experiments, shown that the gene Nanog can stimulate dormant cellular processes that seem to be vital for preventing weak bones, clogged arteries and other telltale signs of aging. The findings might help counteract 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,” said Andreadis.

In order to delay or even reverse the ravages of aging, the human body holds a reservoir of nonspecialized progenitor cells that can regenerate organs. These cells are collectively called “adult stem cells,” and they are in every tissue of the body. Adult stem cells can rapidly respond to tissue damage to regenerate and heal organs and tissues. Unfortunately, as people age, fewer adult stem cells pare able to properly perform their function. This leads to the clinical scenarios associated with aging. Reversing the effects of aging in adult stem cells – re-booting them if you will – can potentially overcome this problem.

Andreadis and his coworkers have previously shown that the capacity of adult stem cells to form muscle and generate force declines with age. Specifically, Andreadis and others examined smooth muscle cells found in arteries, intestines and other tissues. In this new study, grad student Panagiotis Mistriotis introduced a gene called Nanog into aged stem cells. He found that Nanog activated two key cellular pathways that include Rho-associated protein kinase (ROCK) and Transforming growth factor beta (TGF-β). Activation of these two signaling pathways awakens dormant proteins like actin to build the new cytoskeletal networks that adult stem cells need to form contracting muscle cells. 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,” said Andreadis, who noted that introduction of the Nanog 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, Andreadis and his group found that Nanog activated the central regulator of muscle formation, a signaling protein called serum response factor (SRF), which suggests that the same results may be applicable for skeletal, cardiac and other muscle types.

Andreadis and others are now examining potential drugs that can replace or mimic the effects of the Nanog gene. This will allow them to study the consequences of aging inside the body can also be reversed. This could have implications in an array of illnesses, everything from atherosclerosis, high blood pressure, and osteoporosis to Alzheimer’s disease.

This fascinating paper was published here: 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.