Scientists have identified the gene responsible for cellular aging

Biologists know that cellular reprogramming reverses cell aging. But the mechanisms responsible for this process have not yet been discovered. In a recent study, a team of American scientists found proteins that regulate cell aging.

First, a team of biologists from the University of Wisconsin-Madison in Madison, USA, obtained mesenchymal stem/stromal cells (MSCs) from human synovial fluid - found in joints. They were reprogrammed into induced stem cells and brought back to the MSC state, thus rejuvenating them. Finally, the scientists compared the resulting cells with control MSCs that were not experimented on. The findings were published in the journal Sten Cells.

"We found that the activity associated with cellular aging was lower in the reprogrammed cells. This shows that we have reversed the aging process," Dr. Wang-Jiu Di, an author of the study, told the paper.

In the second step, the team analyzed the cells to look for reprogramming-induced changes in gene expression. The biologists found that the expression of the GATA6 protein (which plays an important role in intestinal, lung and heart development) was suppressed in the resulting MSCs. Because of this, the activity of the sonic hedgehog (needed for embryonic development) and FOXP1 (needed for proper development of the brain, heart and lungs) proteins increased. Thus, the GATA6/SHH/FOXP1 pathway appeared to be a key mechanism regulating cellular aging and rejuvenation.

Next, the team examined GATA6 gene expression in response to each of the four Yamanaka factors (transcription factors - or proteins that control mRNA synthesis - associated with key stages of the cell life cycle). OCT4 and KLF4 appeared to regulate GATA6 activity - confirming the results of earlier studies.

"We have shown that mesenchymal stem/stromal cells from synovial fluid change properties and functions after reprogramming. These changes actually rejuvenate the MSCs," Dr. Lee said. He added that their major achievement is the identification of the GATA6/SHH/FOXP1 pathway, a key molecular mechanism controlling cellular aging. "The results show how MSCs age and what they mean for medicine," he concluded.

"The identification of the GATA6/SHH/FOXP1 pathway controlling mesenchymal stem/stromal cell aging is an important discovery," said Ian Nolt, Editor-in-Chief of Sten Cells. Premature aging of MSCs prevents the cells from being used in science and medicine, so the ability to rejuvenate them is extremely valuable.