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.
Buyer Beware
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 only FDA-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.
From infections with no symptoms to why men are more likely to be hospitalized in the ICU and die of COVID-19, new research shows that your genes play a significant role
Early in the pandemic, genetic research focused on the virus because it was readily available. Plus, the virus contains only 30,000 bases in a dozen functional genes, so it's relatively easy and affordable to sequence. Additionally, the rapid mutation of the virus and its ability to escape antibody control fueled waves of different variants and provided a reason to follow viral genetics.
In comparison, there are many more genes of the human immune system and cellular functions that affect viral replication, with about 3.2 billion base pairs. Human studies require samples from large numbers of people, the analysis of each sample is vastly more complex, and sophisticated computer analysis often is required to make sense of the raw data. All of this takes time and large amounts of money, but important findings are beginning to emerge.
Asymptomatics
About half the people exposed to SARS-CoV-2, the virus that causes the COVID-19 disease, never develop symptoms of this disease, or their symptoms are so mild they often go unnoticed. One piece of understanding the phenomena came when researchers showed that exposure to OC43, a common coronavirus that results in symptoms of a cold, generates immune system T cells that also help protect against SARS-CoV-2.
Jill Hollenbach, an immunologist at the University of California at San Francisco, sought to identify the gene behind that immune protection. Most COVID-19 genetic studies are done with the most seriously ill patients because they are hospitalized and thus available. “But 99 percent of people who get it will never see the inside of a hospital for COVID-19,” she says. “They are home, they are not interacting with the health care system.”
Early in the pandemic, when most labs were shut down, she tapped into the National Bone Marrow Donor Program database. It contains detailed information on donor human leukocyte antigens (HLAs), key genes in the immune system that must match up between donor and recipient for successful transplants of marrow or organs. Each HLA can contain alleles, slight molecular differences in the DNA of the HLA, which can affect its function. Potential HLA combinations can number in the tens of thousands across the world, says Hollenbach, but each person has a smaller number of those possible variants.
She teamed up with the COVID-19 Citizen Science Study a smartphone-based study to track COVID-19 symptoms and outcomes, to ask persons in the bone marrow donor registry about COVID-19. The study enlisted more than 30,000 volunteers. Those volunteers already had their HLAs annotated by the registry, and 1,428 tested positive for the virus.
Analyzing five key HLAs, she found an allele in the gene HLA-B*15:01 that was significantly overrepresented in people who didn’t have any symptoms. The effect was even stronger if a person had inherited the allele from both parents; these persons were “more than eight times more likely to remain asymptomatic than persons who did not carry the genetic variant,” she says. Altogether this HLA was present in about 10 percent of the general European population but double that percentage in the asymptomatic group. Hollenbach and her colleagues were able confirm this in other different groups of patients.
What made the allele so potent against SARS-CoV-2? Part of the answer came from x-ray crystallography. A key element was the molecular shape of parts of the cold virus OC43 and SARS-CoV-2. They were virtually identical, and the allele could bind very tightly to them, present their molecular antigens to T cells, and generate an extremely potent T cell response to the viruses. And “for whatever reasons that generated a lot of memory T cells that are going to stick around for a long time,” says Hollenbach. “This T cell response is very early in infection and ramps up very quickly, even before the antibody response.”
Understanding the genetics of the immune response to SARS-CoV-2 is important because it provides clues into the conditions of T cells and antigens that support a response without any symptoms, she says. “It gives us an opportunity to think about whether this might be a vaccine design strategy.”
Dead men
A researcher at the Leibniz Institute of Virology in Hamburg Germany, Guelsah Gabriel, was drawn to a question at the other end of the COVID-19 spectrum: why men more likely to be hospitalized and die from the infection. It wasn't that men were any more likely to be exposed to the virus but more likely, how their immune system reacted to it
Several studies had noted that testosterone levels were significantly lower in men hospitalized with COVID-19. And, in general, the lower the testosterone, the worse the prognosis. A year after recovery, about 30 percent of men still had lower than normal levels of testosterone, a condition known as hypogonadism. Most of the men also had elevated levels of estradiol, a female hormone (https://pubmed.ncbi.nlm.nih.gov/34402750/).
Every cell has a sex, expressing receptors for male and female hormones on their surface. Hormones docking with these receptors affect the cells' internal function and the signals they send to other cells. The number and role of these receptors varies from tissue to tissue.
Gabriel began her search by examining whole exome sequences, the protein-coding part of the genome, for key enzymes involved in the metabolism of sex hormones. The research team quickly zeroed in on CYP19A1, an enzyme that converts testosterone to estradiol. The gene that produces this enzyme has a number of different alleles, the molecular variants that affect the enzyme's rate of metabolizing the sex hormones. One genetic variant, CYP19A1 (Thr201Met), is typically found in 6.2 percent of all people, both men and women, but remarkably, they found it in 68.7 percent of men who were hospitalized with COVID-19.
Lung surprise
Lungs are the tissue most affected in COVID-19 disease. Gabriel wondered if the virus might be affecting expression of their target gene in the lung so that it produces more of the enzyme that converts testosterone to estradiol. Studying cells in a petri dish, they saw no change in gene expression when they infected cells of lung tissue with influenza and the original SARS-CoV viruses that caused the SARS outbreak in 2002. But exposure to SARS-CoV-2, the virus responsible for COVID-19, increased gene expression up to 40-fold, Gabriel says.
Did the same thing happen in humans? Autopsy examination of patients in three different cites found that “CYP19A1 was abundantly expressed in the lungs of COVID-19 males but not those who died of other respiratory infections,” says Gabriel. This increased enzyme production led likely to higher levels of estradiol in the lungs of men, which “is highly inflammatory, damages the tissue, and can result in fibrosis or scarring that inhibits lung function and repair long after the virus itself has disappeared.” Somehow the virus had acquired the capacity to upregulate expression of CYP19A1.
Only two COVID-19 positive females showed increased expression of this gene. The menopause status of these women, or whether they were on hormone replacement therapy was not known. That could be important because female hormones have a protective effect for cardiovascular disease, which women often lose after going through menopause, especially if they don’t start hormone replacement therapy. That sex-specific protection might also extend to COVID-19 and merits further study.
The team was able to confirm their findings in golden hamsters, the animal model of choice for studying COVID-19. Testosterone levels in male animals dropped 5-fold three days after infection and began to recover as viral levels declined. CYP19A1 transcription increased up to 15-fold in the lungs of the male but not the females. The study authors wrote, “Virus replication in the male lungs was negatively associated with testosterone levels.”
The medical community studying COVID-19 has slowly come to recognize the importance of adipose tissue, or fat cells. They are known to express abundant levels of CYP19A1 and play a significant role as metabolic tissue in COVID-19. Gabriel adds, “One of the key findings of our study is that upon SARS-CoV-2 infection, the lung suddenly turns into a metabolic organ by highly expressing” CYP19A1.
She also found evidence that SARS-CoV-2 can infect the gonads of hamsters, thereby likely depressing circulating levels of sex hormones. The researchers did not have autopsy samples to confirm this in humans, but others have shown that the virus can replicate in those tissues.
A possible treatment
Back in the lab, substituting low and high doses of testosterone in SARS-COV-2 infected male hamsters had opposite effects depending on testosterone dosage used. Gabriel says that hormone levels can vary so much, depending on health status and age and even may change throughout the day, that “it probably is much better to inhibit the enzyme” produced by CYP19A1 than try to balance the hormones.
Results were better with letrozole, a drug approved to treat hypogonadism in males, which reduces estradiol levels. The drug also showed benefit in male hamsters in terms of less severe disease and faster recovery. She says more details need to be worked out in using letrozole to treat COVID-19, but they are talking with hospitals about clinical trials of the drug.
Gabriel has proposed a four hit explanation of how COVID-19 can be so deadly for men: the metabolic quartet. First is the genetic risk factor of CYP19A1 (Thr201Met), then comes SARS-CoV-2 infection that induces even greater expression of this gene and the deleterious increase of estradiol in the lung. Age-related hypogonadism and the heightened inflammation of obesity, known to affect CYP19A1 activity, are contributing factors in this deadly perfect storm of events.
Studying host genetics, says Gabriel, can reveal new mechanisms that yield promising avenues for further study. It’s also uniting different fields of science into a new, collaborative approach they’re calling “infection endocrinology,” she says.
New device finds breast cancer like earthquake detection
Mammograms are necessary breast cancer checks for women as they reach the recommended screening age between 40 and 50 years. Yet, many find the procedure uncomfortable. “I have large breasts, and to be able to image the full breast, the radiographer had to manipulate my breast within the machine, which took time and was quite uncomfortable,” recalls Angela, who preferred not to disclose her last name.
Breast cancer is the most widespread cancer in the world, affecting 2.3 million women in 2020. Screening exams such as mammograms can help find breast cancer early, leading to timely diagnosis and treatment. If this type of cancer is detected before the disease has spread, the 5-year survival rate is 99 percent. But some women forgo mammograms due to concerns about radiation or painful compression of breasts. Other issues, such as low income and a lack of access to healthcare, can also serve as barriers, especially for underserved populations.
Researchers at the University of Canterbury and startup Tiro Medical in Christchurch, New Zealand are hoping their new device—which doesn’t involve any radiation or compression of the breasts—could increase the accuracy of breast cancer screening, broaden access and encourage more women to get checked. They’re digging into clues from the way buildings move in an earthquake to help detect more cases of this disease.
Earthquake engineering inspires new breast cancer screening tech
What’s underneath a surface affects how it vibrates. Earthquake engineers look at the vibrations of swaying buildings to identify the underlying soil and tissue properties. “As the vibration wave travels, it reflects the stiffness of the material between that wave and the surface,” says Geoff Chase, professor of engineering at the University of Canterbury in Christchurch, New Zealand.
Chase is applying this same concept to breasts. Analyzing the surface motion of the breast as it vibrates could reveal the stiffness of the tissues underneath. Regions of high stiffness could point to cancer, given that cancerous breast tissue can be up to 20 times stiffer than normal tissue. “If in essence every woman’s breast is soft soil, then if you have some granite rocks in there, we’re going to see that on the surface,” explains Chase.
The earthquake-inspired device exceeds the 87 percent sensitivity of a 3D mammogram.
That notion underpins a new breast screening device, the brainchild of Chase. Women lie face down, with their breast being screened inside a circular hole and the nipple resting on a small disc called an actuator. The actuator moves up and down, between one and two millimeters, so there’s a small vibration, “almost like having your phone vibrate on your nipple,” says Jessica Fitzjohn, a postdoctoral fellow at the University of Canterbury who collaborated on the device design with Chase.
Cameras surrounding the device take photos of the breast surface motion as it vibrates. The photos are fed into image processing algorithms that convert them into data points. Then, diagnostic algorithms analyze those data points to find any differences in the breast tissue. “We’re looking for that stiffness contrast which could indicate a tumor,” Fitzjohn says.
A nascent yet promising technology
The device has been tested in a clinical trial of 14 women: one with healthy breasts and 13 with a tumor in one breast. The cohort was small but diverse, varying in age, breast volume and tumor size.
Results from the trial yielded a sensitivity rate, or the likelihood of correctly detecting breast cancer, of 85 percent. Meanwhile, the device’s specificity rate, or the probability of diagnosing healthy breasts, was 77 percent. By combining and optimizing certain diagnostic algorithms, the device reached between 92 and 100 percent sensitivity and between 80 and 86 percent specificity, which is comparable to the latest 3D mammogram technology. Called tomosynthesis, these 3D mammograms take a number of sharper, clearer and more detailed 3D images compared to the single 2D image of a conventional mammogram, and have a specificity score of 92 percent. Although the earthquake-inspired device’s specificity is lower, it exceeds the 87 percent sensitivity of a 3D mammogram.
The team hopes that cameras with better resolution can help improve the numbers. And with a limited amount of data in the first trial, the researchers are looking into funding for another clinical trial to validate their results on a larger cohort size.
Additionally, during the trial, the device correctly identified one woman’s breast as healthy, while her prior mammogram gave a false positive. The device correctly identified it as being healthy tissue. It was also able to capture the tiniest tumor at 7 millimeters—around a third of an inch or half as long as an aspirin tablet.
Diagnostic findings from the device are immediate.
When using the earthquake-inspired device, women lie face down, with their breast being screened inside circular holes.
University of Canterbury.
But more testing is needed to “prove the device’s ability to pick up small breast cancers less than 10 to 15 millimeters in size, as we know that finding cancers when they are small is the best way of improving outcomes,” says Richard Annand, a radiologist at Pacific Radiology in New Zealand. He explains that mammography already detects most precancerous lesions, so if the device will only be able to find large masses or lumps it won’t be particularly useful. While not directly involved in administering the clinical trial for the device, Annand was a director at the time for Canterbury Breastcare, where the trial occurred.
Meanwhile, Monique Gary, a breast surgical oncologist and medical director of the Grand View Health Cancer program in Pennsylvania, U.S., is excited to see new technologies advancing breast cancer screening and early detection. But she notes that the device may be challenging for “patients who are unable to lay prone, such as pregnant women as well as those who are differently abled, and this machine might exclude them.” She adds that it would also be interesting to explore how breast implants would impact the device’s vibrational frequency.
Diagnostic findings from the device are immediate, with the results available “before you put your clothes back on,” Chase says. The absence of any radiation is another benefit, though Annand considers it a minor edge “as we know the radiation dose used in mammography is minimal, and the advantages of having a mammogram far outweigh the potential risk of radiation.”
The researchers also conducted a separate ergonomic trial with 40 women to assess the device’s comfort, safety and ease of use. Angela was part of that trial and described the experience as “easy, quick, painless and required no manual intervention from an operator.” And if a person is uncomfortable being topless or having their breasts touched by someone else, “this type of device would make them more comfortable and less exposed,” she says.
While mammograms remain “the ‘gold standard’ in breast imaging, particularly screening, physicians need an option that can be used in combination with mammography.
Fitzjohn acknowledges that “at the moment, it’s quite a crude prototype—it’s just a block that you lie on.” The team prioritized function over form initially, but they’re now planning a few design improvements, including more cushioning for the breasts and the surface where the women lie on.
While mammograms remains “the ‘gold standard’ in breast imaging, particularly screening, physicians need an option that is good at excluding breast cancer when used in combination with mammography, has good availability, is easy to use and is affordable. There is the possibility that the device could fill this role,” Annand says.
Indeed, the researchers envision their new breast screening device as complementary to mammograms—a prescreening tool that could make breast cancer checks widely available. As the device is portable and doesn’t require specialized knowledge to operate, it can be used in clinics, pop-up screening facilities and rural communities. “If it was easily accessible, particularly as part of a checkup with a [general practitioner] or done in a practice the patient is familiar with, it may encourage more women to access this service,” Angela says. For those who find regular mammograms uncomfortable or can’t afford them, the earthquake-inspired device may be an option—and an even better one.
Broadening access could prompt more women to go for screenings, particularly younger women at higher risk of getting breast cancer because of a family history of the disease or specific gene mutations. “If we can provide an option for them then we can catch those cancers earlier,” Fitzjohn syas. “By taking screening to people, we’re increasing patient-centric care.”
With the team aiming to lower the device’s cost to somewhere between five and eight times less than mammography equipment, it would also be valuable for low-to-middle-income nations that are challenged to afford the infrastructure for mammograms or may not have enough skilled radiologists.
For Fitzjohn, the ultimate goal is to “increase equity in breast screening and catch cancer early so we have better outcomes for women who are diagnosed with breast cancer.”