Expression of Stem Cell Gene Restores Contractile Function to Aged Muscle Cells

Transplanting a stem cell gene into aged muscle cells reversed many indicators of cellular senescence and completely restored the cells' ability to generate contractile force.

Cellular senescence as a result of aging or progeroid diseases, such as Hutchinson-Gilford progeria syndrome, leads to stem cell pool exhaustion that hinders tissue regeneration and contributes to the progression of age related disorders. Furthermore, the ability of adult stem cells to form muscle and generate force declines with aging.

Investigators at the University at Buffalo (NY, USA) examined the possibility of reversing the aging process by transplanting the NANOG gene into aged muscle cells. NANOG is a transcription factor in embryonic stem cells (ESCs) that is thought to be a key factor in maintaining pluripotency.

The investigators inserted NANOG into cells from three different models of aging: cells isolated from aged donors, cells aged in culture, and cells isolated from patients with Hutchinson-Gilford progeria syndrome. They reported in the July 11, 2016, online edition of the journal Stem Cells that expression of NANOG in senescent or progeroid muscle progenitor cells reversed cellular aging and restored completely the ability to generate contractile force.

NANOG worked this magic by enabling reactivation of the Rho-associated protein kinase (ROCK) and transforming growth factor (TGF)-beta pathways - both of which were impaired in senescent cells. Reactivation of these pathways stimulated dormant proteins (actin) to generate cytoskeletons that adult stem cells need to form contractile muscle cells and activated the central regulator of muscle formation, serum response factor (SRF).

"Our research into Nanog is helping us to better understand the process of aging and ultimately how to reverse it," said senior author Dr. Stelios T. Andreadis, professor of chemical and biological engineering at the University at Buffalo. "Not only does Nanog have the capacity to delay aging, it has the potential in some cases to reverse it."

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