Ageing reversed in old skin cells

gene expression in single cells
Fibroblast cell. Image by Heiti Paves via Wikimedia Commons.

Scientists have reversed ageing in skin cells taken from people who are 80-97 years old. The trick was to turn the skin cells into stem cells and then back into skin cells. This re-programmed the cells and reversed age-related changes allowing the skin cells to make energy more efficiently. 

The energy needed for us to live comes from organelles inside our cells called mitochondria. Mitochondria are essential to keeping us alive but many people believe that mitochondria are also a major cause of ageing. There are two main theories as to how mitochondria cause ageing. The first is that mutations accumulate in DNA inside mitochondria causing the mitochondria to produce less energy. Most of our DNA is housed inside the cell’s nucleus, but mitochondria has its own DNA. The second theory is that when mitochondria produce energy, they also produce waste products called reactive oxygen species (ROS) that damage the cell.

A group of scientists recently tested these theories by comparing skin cells called fibroblasts that were taken from young people (from unborn babies up to 12 year old children) with cells taken from old people (80-97 years old).  They found that old fibroblasts do not make energy as efficiently as young cells. However, the old cells did not have more ROS than young cells and they didn’t have any more mutations in the mitochondrial DNA than young cells. And the mitochondria in the old cells still looked structurally normal.

So the impaired energy production was not due to the two prevailing theories of how mitochondria contribute to cellular ageing. So the scientists postulated that it could instead be due to mutations in DNA in the nucleus of the cell or by epigenetic changes. Epigenetic changes are any changes to our genome that do not change the actual DNA sequence.

To test their new theory, the scientists made stem cells from the young and old fibroblasts, then turned the stem cells back into fibroblasts.  All of these re-made fibroblasts produced energy as efficiently as young cells, even the cells that came from 80-97 year old people. If the age-related drop in energy production was due mutations, it would not have been reversible. This result showed that the ageing changes are caused by epigenetics. But which genes were being targeted by the epigenetic changes?

To work this out, the scientists looked at whether any genes were expressed differently in the young and old fibroblasts. They found that two genes, called GCAT and SHMT21, went down in the old cells and then went back up in the re-programmed cells. Both of these genes make glycine inside cells. So the scientists added glycine to the media that the old fibroblasts were growing in and this also allowed the old cells to make energy more efficiently.

This study is really exciting because it shows that some aspects of ageing can be reversed. This means that ageing is no longer inevitable.

The Scientific Paper:

Hashizume et al. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. Scientific Reports. 2015

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