The Real Science Behind “Anti-Aging” Beauty Products
The beauty market abounds with high-end creams and serums that claim the use of stem cells to rejuvenate aging skin.
Selling on the internet and at department stores like Nordstrom, these products promise "breakthrough" applications to plump, smooth, and "reverse visible signs of aging," and at least one product offers to create a "regenerative firming serum, moisturizer, and eye cream" from customers' own stem cells – for a whopping $1200.
The beauty industry is heavily hyping glimmers of the nascent field of stem cell therapy.
Steeped in clinical-sounding terms like "proteins and peptides from pluripotent stem cells," the marketing of these products evokes a dramatic restoration of youthfulness based on cutting-edge science. But the beauty industry is heavily hyping glimmers of the nascent field of stem cell therapy. So what is real and what's not? And is there in fact a way to harness the potential of stem cells in the service of beauty?
Plant vs. Human Stem Cells
Stem cells do indeed have tremendous promise for treating a wide range of diseases and conditions. The cells come from early-stage embryos or, more commonly, from umbilical cord blood or our own bodies. Embryonic stem cells are considered the body's "master" cells because they can develop into any of our several hundred cell types. Adult stem cells, on the other hand, reside in mature tissues and organs like the brain, bone marrow, and skin, and their versatility is more limited. As an internal repair system for many tissue types, they replenish sick, injured, and worn-out cells.
Nowadays, with some sophisticated chemical coaxing, adult stem cells can be returned to an embryonic-like blank state, with the ability to become any cell type that the body might need.
Beauty product manufacturers convey in their advertising that the rejuvenating power of these cells could hold the key to the fountain of youth. But there's something the manufacturers don't always tell you: their products do not typically use human stem cells.
"The whole concept of stem cells is intriguing to the public," says Tamara Griffiths, a consultant dermatologist for the British Skin Foundation. "But what these products contain is plant stem cells and, more commonly, chemicals that have been derived from plant stem cells."
The plant stem cells are cultured in the lab with special media to get them to produce signaling proteins and peptides, like cytokines and chemokines. These have been shown to be good for reducing inflammation and promoting healthy cell functioning, even if derived from plants. However, according to Griffiths, there are so many active ingredients in these products that it's hard to say just what role each one of them plays. We do know that their ability to replenish human stem cells is extremely limited, and the effects of plant stem cells on human cells are unproven.
"...any cosmetic that is advertised to be anti-aging due to plant stem cells at this time is about as effective as all the skin creams without stem cells."
Whether products containing plant cell-derived ingredients work better than conventional skin products is unknown because these products are not regulated by the U.S. Food and Drug Administration and may rest on dubious, even more or less nonexistent, research. Cosmetics companies have conducted most of the research and the exact formulas they devise are considered proprietary information. They have no incentive to publish their research findings, and they don't have to meet standards imposed by the FDA unless they start using human cells in their products.
"There are biological limits to what you can do with plant cells in the first place," says Griffiths. "No plant stem cell is going to morph into a human skin cell no matter what magic medium you immerse it in. Nor is a plant cell likely to stimulate the production of human stem cells if applied to the skin."
According to Sarah Baucus, a cell biologist, for any type of stem cell to be of any use whatsoever, the cells must be alive. The processing needed to incorporate living cells into any type of cream or serum would inevitably kill them, rendering them useless. The splashy marketing of these products suggests that results may be drastic, but none of these creams is likely to produce the kind of rejuvenating effect that would be on par with a facelift or several other surgical or dermatological procedures.
"Plant stem cell therapy needs to move in the right direction to implement its inherent potential in skin care," researchers wrote in a 2017 paper in the journal Future Science OA. "This might happen in the next 20 years but any cosmetic that is advertised to be anti-aging due to plant stem cells at this time is about as effective as all the skin creams without stem cells."
From Beauty Counter to Doctor's Clinic
Where do you turn if you still want to harness the power of stem cells to reinvigorate the skin? Is there a legitimate treatment using human cells? The answer is possibly, but for that you have to switch from the Nordstrom cosmetics counter to a clinic with a lab, where plastic surgeons work with specialists who culture and manipulate living cells.
Plastic surgeons are experts in wound healing, a process in which stem cells play a prominent role. Doctors have long used the technique of taking fat from the body and injecting it into hollowed-out or depressed areas of the face to fill in injuries, correct wrinkles, and improve the face's curvature. Lipotransfer, or the harvesting of body fat and injecting it into the face, has been around for many years in traditional plastic surgery clinics. In recent years, some plastic surgeons have started to cull stem cells from fat. One procedure that does just that is called cell-assisted lipotransfer, or CAL.
In CAL, adipose tissue, or fat, is harvested by liposuction, usually from the lower abdomen. Fat contains stem cells that can differentiate into several cell types, including skin, muscle, cartilage, and bone. Fat tissue has an especially stem cell-rich layer. These cells are then mixed with some regular fat, making in effect a very stem cell-rich fat solution, right in the doctor's office. The process of manipulating the fat cells takes about 90 to 110 minutes, and then the solution is ready to be injected into the skin, to fill in the lips, the cheeks, and the nasolabial folds, or the deep folds around the nose and mouth.
Unlike regular fat, which is often injected into the face, some experts claim that the cell-enriched fat has better, longer-lasting results. The tissue graft grows its own blood vessels, an advantage that may lead to a more long-lasting graft – though the research is mixed, with some studies showing they do and other studies showing the complete opposite.
For almost all stem cell products on the market today in the U.S., it is not yet known whether they are safe or effective, despite how they are marketed.
One of the pioneers in CAL, a plastic surgeon in Brazil named Dr. Aris Sterodimas, says that the stem cells secrete growth factors that rejuvenate the skin -- like the plant stem cells that are used in topical creams and serums. Except that these cells are human stem cells and hence have inherently more potential in the human body.
Note that CAL doesn't actually result in large numbers of fresh, new replacement cells, as might be imagined. It's simply fat tissue treated to make it richer in stem cells, to have more of the growth-inducing proteins and peptides delivered to the dermis layer of the skin.
Sterodimas works alongside a tissue engineer to provide CAL in his clinic. He uses it as a way to rebuild soft tissues in people disfigured by accidents or diseases, or who are suffering the after-effects of radiation treatments for cancer.
Plastic surgeons get plenty of these patients. But how widespread is CAL for beauty purposes? Sterodimas says that he regularly performs the procedure for Brazilians, and it's widely available in Europe and Japan. In the U.S., the procedure hasn't taken off because there is no FDA approval for the various methods used by different doctors and clinics. A few major academic centers in the U.S. offer the treatment on a clinical trials basis and there are several trials ongoing.
But there is a downside to all lipotransfers: the transplanted fat will eventually be absorbed by the body. Even the cell-enriched fat has a limited lifespan before reabsorption. That means if you like the cosmetic results of CAL, you'll have to repeat the treatment about every two years to maintain the plumping, firming, and smoothing effects on the skin. The results of CAL are "superior to the results of laser treatments and other plastic surgery interventions, though the effect is not as dramatic as a facelift," says Sterodimas.
For almost all stem cell products on the market today in the U.S., it is not yet known whether they are safe or effective, despite how they are marketed. There are around 700 clinics in the U.S. offering stem cell treatments and up to 20,000 people have received these therapies. However, the onlyFDA-approved stem cell treatments use cells from bone marrow or cord blood to treat cancers of the blood and bone marrow. Safety concerns have prompted the FDA to announce increased oversight of stem cell clinics.
As for CAL, most of the clinical trials so far have been focused on using it for breast reconstruction after mastectomy, and results are mixed. Experts warn that the procedure has yet to be proven safe as well as effective. It's important to remember that this newborn science is in the early stages of research.
One question that has also not been definitively settled is whether the transplanted stem cells may give rise to tumors — a risk that is ever-present any time stem cells are used. More research is required to assess the long-term safety and effectiveness of these treatments.
Given the lack of uniform industry standards, one can easily end up at a clinic that overpromises what it can deliver.
In the journal Plastic Reconstruction Surgery in 2014, Adrian McArdle and a team of Stanford University plastic surgeons examined the common claims of CAL's "stem cell facelifts" being offered by clinics across the world. McArdle and his team write: "…the marketplace is characterized by direct-to-consumer corporate medicine strategies that are characterized by unsubstantiated, and sometimes fraudulent claims, that put our patients at risk." Given the lack of uniform industry standards, one can easily end up at a clinic that overpromises what it can deliver.
But according to McArdle, further research on CAL, including clinical trials, is proceeding apace. It's possible that as more research on the potential of stem cells accrues, many of the technical hurdles will be crossed.
If you decide to try CAL in a research or clinical setting, be forewarned. You will be taking part in a young science, with many unknown questions. However, the next time someone offers to sell you stem cells in a jar, you'll know what you're paying for.
The study and copying of nature’s models, systems, or elements to address complex human challenges is known as “biomimetics.” Five hundred years ago, an elderly Italian polymath spent months looking at the soaring flight of birds. The result was Leonardo da Vinci’s biomimetic Codex on the Flight of Birds, one of the foundational texts in the science of aerodynamics. It’s the science that elevated the Wright Brothers and has yet to peak.
Today, biomimetics is everywhere. Shark-inspired swimming trunks, gecko-inspired adhesives, and lotus-inspired water-repellents are all taken from observing the natural world. After millions of years of evolution, nature has quite a few tricks up its sleeve. They are tricks we can learn from. And now, thanks to some spider DNA and clever genetic engineering, we have another one to add to the list.
The elusive spider silk
We’ve known for a long time that spider silk is remarkable, in ways that synthetic fibers can’t emulate. Nylon is incredibly strong (it can support a lot of force), and Kevlar is incredibly tough (it can absorb a lot of force). But neither is both strong and tough. In all artificial polymeric fibers, strength and toughness are mutually exclusive, and so we pick the material best for the job and make do.
Spider silk, a natural polymeric fiber, breaks this rule. It is somehow both strong and tough. No surprise, then, that spider silk is a source of much study.The problem, though, is that spiders are incredibly hard to cultivate — let alone farm. If you put them together, they will attack and kill each other until only one or a few survive. If you put 100 spiders in an enclosed space, they will go about an aggressive, arachnocidal Hunger Games. You need to give each its own space and boundaries, and a spider hotel is hard and costly. Silkworms, on the other hand, are peaceful and productive. They’ll hang around all day to make the silk that has been used in textiles for centuries. But silkworm silk is fragile. It has very limited use.
The elusive – and lucrative – trick, then, would be to genetically engineer a silkworm to produce spider-quality silk. So far, efforts have been fruitless. That is, until now.
We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
Junpeng Mi and his colleagues working at Donghua University, China, used CRISPR gene-editing technology to recode the silk-creating properties of a silkworm. First, they took genes from Araneus ventricosus, an East Asian orb-weaving spider known for its strong silk. Then they placed these complex genes – genes that involve more than 100 amino acids – into silkworm egg cells. (This description fails to capture how time-consuming, technical, and laborious this was; it’s a procedure that requires hundreds of thousands of microinjections.)
This had all been done before, and this had failed before. Where Mi and his team succeeded was using a concept called “localization.” Localization involves narrowing in on a very specific location in a genome. For this experiment, the team from Donghua University developed a “minimal basic structure model” of silkworm silk, which guided the genetic modifications. They wanted to make sure they had the exactly right transgenic spider silk proteins. Mi said that combining localization with this basic structure model “represents a significant departure from previous research.” And, judging only from the results, he might be right. Their “fibers exhibited impressive tensile strength (1,299 MPa) and toughness (319 MJ/m3), surpassing Kevlar’s toughness 6-fold.”
A world of super-materials
Mi’s research represents the bursting of a barrier. It opens up hugely important avenues for future biomimetic materials. As Mi puts it, “This groundbreaking achievement effectively resolves the scientific, technical, and engineering challenges that have hindered the commercialization of spider silk, positioning it as a viable alternative to commercially synthesized fibers like nylon and contributing to the advancement of ecological civilization.”
Around 60 percent of our clothing is made from synthetic fibers like nylon, polyester, and acrylic. These plastics are useful, but often bad for the environment. They shed into our waterways and sometimes damage wildlife. The production of these fibers is a source of greenhouse gas emissions. Now, we have a “sustainable, eco-friendly high-strength and ultra-tough alternative.” We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
We shouldn’t get carried away. This isn’t going to transform the textiles industry overnight. Gene-edited silkworms are still only going to produce a comparatively small amount of silk – even if farmed in the millions. But, as Mi himself concedes, this is only the beginning. If Mi’s localization and structure-model techniques are as remarkable as they seem, then this opens up the door to a great many supermaterials.
Nature continues to inspire. We had the bird, the gecko, and the shark. Now we have the spider-silkworm. What new secrets will we unravel in the future? And in what exciting ways will it change the world?
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.