It’s tempting to think of skin as a simple protective layer. But that’s just the beginning. Skin is a fantastically complex organ. It cools us and keeps us warm. It helps us sense the external environment. And it is self-repairing, thanks to the tireless work of armies of molecular machines that repair damage, rehydrate tissue and stimulate new cell growth, much of this work completed at night.
Just how this repair work is coordinated and controlled is a heavily studied topic. In recent years, researchers have discovered a class of molecules in the body that help control how genes work, translating the impact of diet and lifestyle into physical effects on the aging process, including in skin.
Epigenetics is the study of the way genes are controlled, or expressed, in the body. Our genes are influenced by a range of factors in the environment. Whereas some biological markers can switch genes on and off, a class of molecules known as microRNAs act almost like dimmer switches, tuning the activity of a gene up or down. These epigenetic changes are thought to play important roles in human health, including in ageing.
Epigenetic signals
This class of molecules plays a vital role in keeping us healthy, but also seems to influence how skin ages, says Nadine Pernodet, vice president of research and development in skin biology and bioactives at Estée Lauder. By understanding the role of these molecules in young skin cells, she says we can hope to unveil critical processes to support the repair of older skin cells.
“If we understand what’s occurring naturally in the skin, and which epigenetic signals are firing that create damage or support repair, it would give us more tools and power to help slow down the ageing process and to help to repair the look of skin over time,” says Pernodet.
For the past thirteen years, her group’s work has focused on epigenetics and skin. All cells in your body contain the same set of DNA but end up working in very different ways. For example, a liver cell looks and acts very differently than a brain cell even though they have the exact same DNA. And the reason they act differently is because of epigenetics. Therefore, it is imperative to specifically study the cell type of interest.
Thousands of these tiny microRNA molecules have been identified in humans, and they are thought to target over 60 per cent of human genes, says Pernodet. And the molecules can impact genes in multiple ways and can trigger different responses in different cell types.
MicroRNAs influence how cells develop and die, as well as how our bodies control metabolism and respond to stress, among other things. And while the field is still young, these molecules are being explored as potential markers to diagnose some diseases and treat others. “Now that scientists are looking at these in different fields, we are seeing that microRNAs are involved in basically everything,” says Pernodet.
When Pernodet and her colleagues set out to look for microRNAs that might play a role in skin ageing, they looked at how levels of microRNAs change as we age. At the same time, they were also interested in circadian rhythms – specifically, how biological processes in the skin change with the time of day.
Previous research suggests that our skin provides a more effective barrier during the day, when its key role is protecting us from environmental damage, whether that be from UV light, pollution or anything else we might encounter that could potentially cause damage. Overnight, the focus is on repairing damage that has occurred during the day, says Pernodet. “Skin naturally produces proteins and lipids to rebuild its barrier to be ready for the next morning,” she says.
“Unfortunately, this beautiful, perfect machinery becomes dysregulated due to exposure to pollution, stress, lack of sleep, or ageing,” says Pernodet. So her team set out to find microRNAs that are not only linked to ageing, but which are also linked to the skin’s circadian rhythm.
Pernodet’s team have identified a microRNA that appears to do just that. They began by looking at the levels of 80 known microRNAs in skin cells taken from people aged 19, 27, 40 and 62. One molecule jumped out. Levels of mir-146a appeared to decline with age. But the molecule also seemed to interact with a gene called PER1, which is known to code for a protein that helps maintain circadian rhythms.
Anti-ageing markers
Further research revealed that levels of mir-146a are linked to a host of anti-ageing markers in skin. As levels of mir-146a decline, so do levels of collagen – a protein key to skin’s structure. At the same time, with less mir-146a, skin cells appear less able to respond to the damaging effects of UV light, and less able to repair cellular damage, says Pernodet.
In attempting to halt this trend in older skin, Pernodet’s team worked with a collaborator to identify compounds that might increase mir-146a levels. The search identified an extract from the African baobab tree Adansonia digitata.
When Pernodet’s team applied this extract to skin cells in the lab, they saw dramatic results. Within 48 hours of treatment, 62-year-old cells started to show levels and distribution of mir-146a closer to those of 19-year-old cells. Treated cells were also better at regenerating after 7 days of treatment. “This in vitro testing showed cell numbers increased by more than 40 percent, which is going to help the skin visibly rebuild over time,” says Pernodet.
Pernodet’s team then combined the extract with other repair ingredients. The resulting combination was shown in in vitro testing to improve the ability of 62-year-old cells to recover from cellular damage caused by UV light, and to increase significantly the production of collagen.
This area of science is just emerging. Pernodet plans to identify other microRNAs that might play a role in skin ageing and will soon begin collaborating with a research team at the University of California Irvine to that effect. “We identified this one, but I’m sure there are others to discover,” she says. “I think we are going to see an explosion in this field – not only for us in the cosmetics industry, but all over.”Source:Web
