© 2016 A*STAR Genome Institute of Singapore

Unlocking the mystery of an age-old secret

23 Feb 2016

A quest to unravel the secrets of cloning has led to a greater understanding of how cells age

An egg cell, or 'oocyte'.

An egg cell, or ‘oocyte’.

© 2016 A*STAR Genome Institute of Singapore

It’s not quite the mythical elixir of youth, but A*STAR scientists have found a way to control aging at a cellular level. Researchers have pinpointed the gene in human egg cells that can block the process that causes cells to age.

The discovery could be the first step toward  rejuvenating dying tissues and organs in the body, says Ng Shyh-Chang from the A*STAR Genome Institute of Singapore.

The breakthrough was made as Ng and his team tried to unravel the mystery behind the 1996 cloning of Dolly the sheep, who was created when stem cell researchers combined the nucleus of an adult cell with an egg cell. While scientists knew the egg cytoplasm contained special factors that can reprogram adult cells into embryonic stem cells, the underlying mechanism remained unclear.

“When you put a cell nucleus into an egg something magical happens, but people don’t understand why it works,” he says. This lack of knowledge was highlighted in 2006 when Japanese researcher, Shinya Yamanaka, showed that any adult cell could be turned into a stem cell through a process known as induced pluripotent stem cell reprogramming (iPSC). However, Ng says there was a vast difference in the effectiveness of the iPSC reprogramming and the cells it produced compared with the approach that created Dolly. Ng believed a better understanding of what happened when Dolly was cloned could resolve these problems.

“We wanted to revisit the old system in pioneering cloning and find what other genes and factors in the egg can facilitate this reprogramming process, what helps it become more efficient, more accelerated,” Ng says.

Their work revealed old mitochondria — the oxygen-consuming engines in cells — blocked cellular rejuvenation. But they also found that the gene, Tcl1, which is highly abundant in egg cytoplasm, binds to a mitochondrial enzyme PnPase that regulates mitochondrial growth. By increasing the amount of Tcl1 in the egg, the researchers were able to control the aging rate of the cells.

“We found if we suppress mitochondrial growth, we could set the stage for the cells to be rejuvenated back to their embryonic state,” says Ng.

He says the findings have direct implications in generating better stem cells without the ethical implications associated with using cells from human embryos. Ng says the findings could also be the important ’first step’ in reversing the aging process in human organs such as the heart.

“To figure out how to rejuvenate cells that are on their way to death and rescue them back would be the holy grail,” he says.

The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore.

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Khaw, S.-L., Chua, M.-W, Koh, C.-G., Lim, B., Ng, S.-C. Oocyte factors suppress mitochondrial polynucleotide phosphorylase to remodel the metabolome and enhance reprogramming. Cell Reports 12, 1080–1088 (2015). | Article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature