Corneocytes form a protective barrier at the skin's outermost surface (left). Heatmap depicting changes in metabolite levels with age or time (PM/AM). Red: significantly up. Green: significantly down. White: no significant change.Credit: Estée Lauder
Day after day, our skin endures a barrage of harsh ultraviolet radiation, irritating chemicals and toxic ozone gas. For an organ not much thicker than the head of a pin, that assault is a lot to take, and over time it can accelerate visible aging. Most assumed that this aging was inevitable, but a new series of studies seems to indicate that age may not be destiny after all.
By monitoring subtle shifts in the biochemical composition of skin cells, researchers at Estée Lauder, a global leader in prestige beauty, have revealed that, like many other parts of the body, skin has a daily rhythm that tends to weaken with age. Scientists have shown that skin can be returned to a more youthful rhythm and that visible signs of aging could be reduced.
“The work provides a whole new view of how skin should be looked at,” Paolo Sassone-Corsi, Director of the Center for Epigenetics and Metabolism at the University of California, Irvine, says. “It is not an inert tissue, but instead is extremely active in its metabolism.”
The Hidden Rhythm of Skin
Since the 1970s, scientists have known that the characteristics of young and healthy skin change over the course of the day. In waking hours, skin acts as a barrier to all manner of external threats, from radiation to irritants, leaving it taut and dry. At night, skin repairs the damage sustained in the previous day. By morning, it is softer, more hydrated and ready to face the day’s irritants as a restored barrier.
For Estée Lauder, this biological rhythm begged better understanding. In 2007 the company recruited Nadine Pernodet from the Materials Science and Engineering department of Stony Brook University, where she was investigating how skin function is altered by epigenetic changes—heritable changes in tissue that do not involve altering the cell’s DNA sequence. At that time, there was continuing research into the science of circadian rhythms, including those of various organs. Three researchers were awarded the 2017 Nobel Prize in Physiology or Medicine for work in this area. But little was understood about the circadian rhythms of skin.
At first, Pernodet and her team studied human skin cells grown from younger and older subjects in the lab. They found evidence of circadian rhythms in lab-grown younger cells, but not in older ones, an indication that repair efficiency degrades with age. That insight helped guide the reformulation of Estée Lauder’s Advanced Night Repair Synchronized Recovery Complex in 2009. But, for Pernodet, questions remained.
She followed up by identifying several other cellular processes that fluctuate according to a circadian rhythm. These included a natural cellular “recycling” process that removes cellular “debris”, such as damaged proteins and lipids, and other natural rhythmic skin activities that produce new proteins, including collagen and a protein that restores the skin barrier.
Next, she needed a method to validate her in vitro findings in vivo. She found it in metabolomics, a method that allows scientists to measure the presence of hundreds of metabolites—small compounds produced in the course of cellular metabolism—at any given time. Paired with analytical software, the data can provide a detailed snapshot of a tissue’s metabolism.
“The beauty of metabolomics is that it takes into account everything—not only your genetics, but your microbiome, where you live, what you do, your age, and more, to give you an overall image of what’s happening in your skin at any time,” Pernodet says.
Pernodet first worked with a leading metabolomics company over several years to develop a noninvasive method to quantify skin metabolites. Scientists would place a strip of special tape on someone’s skin, pull it off, and then remove the attached skin metabolites for analysis.
In an unpublished internal Estée Lauder study, presented in June at the World Congress of Dermatology, Pernodet and her team used this method to identify several hundred metabolites that influence skin appearance in Caucasian women under 25. They found that more than 60 percent of them cycle strongly and consistently throughout the day. In Caucasian women over 60, however, less than 20 percent of those metabolites oscillated in the same rhythm.
Network diagrams as generated by the STITCH database. Nodes are metabolites identified on the list of significantly rhythmic metabolites for each cohort. Edges are either association via literature or known chemical-chemical interactions. In the young cohort, rhythmic metabolites are more connected. In the mature cohort, they are less connected. In the mature cohort that underwent treatment, rhythmic metabolites re-established critical connections1. Credit: Estée Lauder
This work was the first to use metabolomics to investigate the difference between youthful and aging facial skin. The results revealed for the first time that certain skin metabolites oscillated, following a circadian rhythm, and that those oscillations grow weak and more erratic with age, impeding repair, Pernodet says.
In the same study, Pernodet’s team evaluated a skin-treatment that contained a peptide designed to support skin’s natural renewal and synchronization. The results indicated that when women over 60 applied it to their face daily for two months, it helped to promote skin’s natural rhythm through the restoration of more than two dozen metabolites. It also helped stimulate powerful natural protection mechanisms to fight oxidative damage from environmental irritants, and it positively impacted skin biomarkers associated with visible skin damage.
In aging skin, “protection and repair mechanisms are a little bit lazy,” Pernodet says. “Now not only are you waking them up, you’re telling them at which time they have to work to get optimal results.”
As goes skin, so goes the body
The applications for a metabolomic test strip could extend far beyond the skin. Metabolites, Sassone-Corsi says, are an indicator for other health conditions too. In liver, muscle, fat, brain and gut “almost every class of metabolite, including amino acids, carbohydrates, and lipids, oscillates dramatically.” What’s more, “there’s coordination between different tissues, and the language they speak is metabolic.”
Although scientists haven’t proven that skin’s metabolic rhythms are also coordinated with internal organs, Sassone-Corsi suspects that they are. If so, a quick tape-strip skin test could offer a view not just of skin activity and rhythm as it cycles through the day, but also organ health. That, in turn, “might develop into wonderful future approaches for personalized medicine.”