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Coming of Age: Skin Care Research and Aging

Cutting-edge research is transforming the way scientists approach skin care and the aging process.

About 15 years ago scientists made a stunning discovery: There are genes that control aging. This was followed by another significant finding: These genes, called sirtuins, could be activated to extend life span—a phenomenon that has since been proven in yeast, fruit flies, a tiny worm and mice. What’s more, the animals in these studies didn’t just go on to live longer lives, they went on  to live healthier lives, with less diabetes, less weight gain on high lipid diets and better allover cardiovascular well-being.

While life-span extension hasn’t yet been achieved in humans, it’s being studied at the cellular level with promising results. The implications for a longer, healthier life are clear. Such research has equally as significant consequences for the beauty industry. As the science of aging has progressed, cosmetics firms have benefited with an increasingly deeper understanding of how the skin ages and have been able to harness that information to develop ever more sophisticated products.

“In the last 20 years, there has been essentially a revolution in research on aging,” says Tom Mammone, executive director of research and development for Clinique Worldwide. “The excitement in the field is that we can do something: We can’t stop the aging process, but we can slow it down.”

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While most of us regard aging skin in terms of its effects—lines, wrinkles, hyperpigmentation and lack of tone, to name a few—scientists are focused on the shifts that occur at the cellular level. It’s here they’ve identified the seven distinct signs that cause aging, according to Eric Perrier, executive vice president of R&D at LVMH Parfums et Cosmétiques: Cell loss and tissue atrophy, nuclear mutations (that is, changes to the cell nucleus), mitochondria mutations (changes to the parts of the cells that contain genetic material), death resistant cells, tissue stiffening, extracellular aggregates and intracellular aggregates.

To counter these effects virtually every major beauty brand is looking at various aspects of this genetic aging process, conducting state-of-the-art research often in partnership with leading academic institutions, hospitals and biotech and pharmaceutical companies.

At Procter & Gamble, for example, a major focus since the late Nineties has been on gene expression profiling technologies—measuring the activity of thousands of genes simultaneously—to gain a better understanding of skin biology as a whole and, in particular, how skin changes as a result of its environment and the natural aging process.

Where once upon a time a large sample of skin had to be biopsied and sectioned for study (a process that might yield info on one or two genes at a time), now a microscopic bit can deliver information on over 40,000 genes in a single experiment and up to 1.3 million genes a week. The result is faster and more precise information about the skin than ever before.

Among the applications of this information: the detection of cellular signaling pathways, insight into how the skin interacts with its environment, the sun and ingredients applied to it, a deeper understanding of the structures of the skin and the identification of the signatures of healthy skin. According to Jay Tiesman, principal scientist in global biotechnology, who leads the genomics team in providing biotech expertise across P&G, “As the database grows of what a healthy [gene] signature looks like, we can more rapidly create new and better products that will help us in that direction.”

Tiesman’s colleague, Rosemarie Osborne, principal scientist in beauty biology specializing in skin aging at P&G, has pioneered the use of in vitro human skin equivalents at the company. Originally developed to serve as alternatives to animal testing in safety assessments for chemicals and product formulations, Osborne’s human skin models are now being used to measure irritant responses of skin and also to better understand the skin’s response to ingredients commonly used in antiaging and other personal care products. Her team uses these same multilayer skin cultures to assess other skin parameters, such as moisturization, pigmentation and the production of collagen.

These artificial skin cultures help to develop a better understanding of the efficacy of skin care products and ingredients, says Osborne. This, along with the genomics research being performed at the company, is helping its researchers pinpoint what is happening to the skin as it ages. Among their recent findings, the skin’s barrier is profoundly damaged in aged skin. “This primary change causes the skin to use all its energy to repair the barrier instead of repairing deeper damage, like collagen and elastin deterioration,” says Osborne. “Improving the barrier will allow the skin to repair its deeper layers.”

In the past, researchers at the Estée Lauder Cos. had concentrated their antiaging work on protection and repair: Protecting the skin from damage caused by the external environment and repairing damage caused by UV light. Almost five years ago that focus shifted to genetic aging and, specifically, sirtuins, the genes that impact longevity, with Lauder working in conjunction with research groups at Harvard and the Massachusetts Institute of Technology. The goal at the time was to activate sirtuins artificially, to induce an increase in longevity without putting the cells in caloric deprivation. Resveratrol, from grapes, was one molecule found to successfully trigger this false alarm response in the cells and lead to an increase in their life span.

In addition to the cells living longer, researchers found those cells also became more resistant to  DNA damage. “Activating the sirtuin increased the duration of each cell cycle, allowing the cells more time to repair,” says Daniel Maes, senior vice president of global research and development at Estée Lauder. “This led us to the belief that it is absolutely necessary not to speed up the cells but to slow them down so they can repair themselves of damage they’re exposed to.”

Going forward, Lauder is continuing to exploit the impact of sirtuins on skin cells and looking at activating others cells so they, too, have better opportunity to repair.

Like its sister brand, scientists at Clinique are focused on continuing research into sirtuin genes (there are seven) and molecules beyond resveratrol that trigger their activation. They, along with the 20 outside research collaborators they partner with, are also looking beyond these established longevity genes. “Sirtuins just scratch the surface,” says Mammone. “There’s a whole other body of longevity genes having to do with insulin and insulinlike pathways in the body that have been shown to influence aging.”

Mammone is also keeping close tabs on rapidly expanding stem cell research and, specifically, the adult stem cells in the skin that divide and make new skin on a monthly basis. “We want to know how they change with age and how we [can] help them do a better job at it,” he says.

Another area of interest for Clinique is pharmacogenetics—or the interactions of compounds based on one’s genetic profile. Basically, instead of picking products based on the condition of one’s skin—dry, oily, sun sensitive, etc.—the brand foresees the day when a customer will be able to get a whole skin care regime customized for her according to her genes. It “will result in more targeted, not to mention safer, products for our consumers,” says Mammone.

In its quest for a deeper understanding of the skin, scientists at L’Oréal partner with approximately 100 universities, hospitals and public research institutions worldwide. L’Oréal research draws from the fields of cellular biology, molecular biology and, increasingly, skinomics—a term it coined to describe its stateof- the-art tools of research including genomics, transcriptomics (the study of gene activity and expression) and proteomics (the study of proteins). For skinomics and aging, in particular, L’Oréal Research has had a long-term partnership with Hôpital Saint-Louis in Paris and Centre Hospitalier Universitaire Laval in Quebec.

Recent skinomics research comparing the signatures of young and old skin resulted in the identification of gene expression and protein fingerprints. First, researchers determined gene activity in young skin compared with aged skin. “They found that in response to a skin surface aggression, the onset of gene activity linked to skin barrier recovery was slower in old skin than in young skin,” says George Rivera, senior scientific liaison for L’Oréal Laboratories. A clinical study of the link between the gene and protein signatures led to the identification of active ingredients that are able to modify the protein signature of aged skin, so that it more closely approximates that of young skin. These ingredients will be formulated in future antiaging products, says the company.

Going forward, all L’Oréal research will begin with the assumption that by increasing levels of proteins that reduce over time one can work to approach the protein signature of younger skin. “Skinomics gave us access to the protein signatures of young and aged skin and uncovered approaches to reverse the skin status,” sums up Patricia Pineau, research communication director at L’Oréal.

Researchers at Dior and its parent company LVMH Moët Hennessy Louis Vuitton are investing significant resources into gene expression and longevity research, too, but another major focus is on stem cells. Embryonic stem cells—derived from human embryos and having the capacity to transform into any type of tissue—are generally unusable for ethical reasons. On the other hand, adult stem cells—found in all human organs and dedicated to tissue renewal and repair (or, with respect to skin, the making of new skin)—are fair game and the skin contains many more of them than expected.

Unfortunately, their number and capacity to divide and self-renew decreases with age and recent studies have shown they’re especially sensitive to oxidative stress. “We need to protect them so they don’t lose strength and power with age” says LVMH’s Perrier. This is especially challenging since stimulating stem cells tends to induce a proliferation of them, which in turn causes them to lose their ability to regenerate tissue. Adding insult to injury, so to speak, adult stem cells are notoriously difficult to identify, extract and cultivate in vitro, making research of them even more taxing.

Still, thanks to their capacity for regeneration, adult stem cells in the skin offer great potential for cosmetic application, says Perrier. “We think stem cells are very important and will provide much more knowledge and understanding of the skin,” he says, “but we’re at the beginning of this work, and have to proceed in an intelligent way.”

Scientists at Chanel base all their antiaging research on two principles: 1) That aging is not coded in the genome, but involves the coordination and interaction of different gene functions and 2) that it’s a complex process influenced by multiple interacting factors including genetics, biology, behavior and social and cultural aspects of the human environment.

To that end, the company is partnering with the University of Pennsylvania on its genomics research, Toulouse University in France on gene expression technology and for stem cells, a university near London they decline to name due to the proprietary and confidential nature of the work. Current areas of interest include research in cellular aging (specifically, identifying the right markers of  cutaneous stem cells versus regular skin cells in the dermis), cell-cell adhesion (that is, looking at how growth factors and proteins act as messengers of communication between cells) and glycomics, when natural sugar molecules bind to protein fibers in the skin and cause them to become stiff and brittle.

“We know sugars have a strong deregulation function on the skin and are working on ways to reverse glycation,” says Christian Mahé, senior vice president of research and technology at Chanel. “But we also believe these sugars are linked to communication between cells and could be vectors for enhancing properties of the messenger, so it’s a huge topic for us in the next few years.” An upcoming European launch from the company will deal directly with counteracting glycation.

Mahé is also interested in skin-barrier function, not only as it relates to hydration, but aging as well. “We need to understand the key enzymes and proteins that deliver the best barrier function, to see how this quality of barrier function can act on the cellular properties of the skin,” he says.
But that’s not all. Mahé is eager to highlight the psycho-sensorial aspect of this research. “To have a well-defined barrier is important, but as important is how we feel about having a nice barrier. Advances in cognitive sciences mean the sensorial and emotional effect of our products can be amplified.”

So what’s next? According to researchers, more targeted, more effective and, eventually, more customized therapies. “We can imagine the ultraprecise and ultrarapid analysis of the quality of the skin, such that we can propose products especially for that person,” says Mahé. “The products will be just the right combination of technology, efficacy and simplicity.”