‘New approaches to prevention and treatment’ was the title of this year’s Anti-Ageing Skin Care Conference, which took place at the Royal Collage of Physicians, London, from 7-8 June. Bringing together the world’s leading authorities on skin care, the event began with an address from Conference Chairman Jack Ferguson of Skinnovation Ltd, who asked attendees: “What can you see as being the future of skin care for ageing skin?”
Day one was top and tailed by two keynotes, delivered by Jean Krutmann, Professor of Dermatology and Environmental Medicine and Director of the IUF Leibniz Research Institute for Environmental Medicine in Germany, and Professor Suresh Rattan of the Laboratory of Cellular Ageing, Department of Molecular Biology & Genetics, Aarhus University, Denmark.
Krutmann said that, in recent years, extrinsic skin ageing has been used synonymously with photoageing, which he noted is not the complete truth, as visible light, infrared-A, tobacco smoke and air pollution all have an impact on how our skin ages.
Focusing on air pollution generally and particulate matter (PM) and nitrogen oxide (NO2) specifically, Krutmann flagged up a study published in 2010 on airborne particle exposure and extrinsic skin ageing in urban-dwelling German women aged over 50, which found that the higher the soot concentration the higher the risk of developing pigment spots (lentigines) on cheeks.
Inspired by this, Aarhus University joined forces with two Chinese universities in 2012 for an ongoing collaboration studying Han Chinese women from the industrial Taizhou area, as well as urban German women, looking at both exposure to PM but also to NO2 (primarily from traffic pollution). An increase of 10μm/m2 in NO2 was associated with 25% more pigment spots on the cheeks of German women and with 24% more pigment spots on the cheeks of Chinese women older than 50 years.
“This tells us two things,” said Krutmann. “It’s not only the particles that cause the problem but also NO2.” However, he noted that these studies do not address whether NO2 by itself can have an effect.
He then presented fresh research into gene-environment interactions, focusing on the MC1R gene (associated with lentigines) and the aryl hydrocarbon receptor/aryl hydrocarbon receptor repressor genes (hypothesised to be involved in pollution-induced lentigines formation). The individual’s MC1R genetic risk score was found not to have a significant effect on the formation of PM- or NO2-induced lentigines. However, the risk score for AHR/AHRR was found to have a “very strong, significant effect” on PM2.5- and PM10-, although not NO2-induced lentigines on cheeks, meaning “women with a high genetic risk of AHR/AHRR develop more lentigines on their cheeks after exposure to air pollution”, he told attendees.
Possible mechanisms were discussed, with Krutmann hypothesising that polyaromatic hydrocarbons on the surface of carbon particles could penetrate human skin and activate the AHR, supported by ex vivo skin models indicating that “topical application of diesel can increase ARH activation in human skin”. A complementary research programme indicated that topical application of diesel exhaust particles can increase ARH singling in human skin.
“At the end of the day, how can we use this information to develop a solution,” asked Krutmann. In answer, he presented a novel cosmetic strategy from Symrise (see box), which acts as an AHR-antagonist in human keratinocytes and which is a hot candidate for addressing pollution-induced ageing.
Mitochondrial DNA damage
The relationship between oxidative stress – induced by pollution, sunlight and diet – and the skin was explored by Professor Mark Birch-Machin of the Faculty of Medical Sciences at Newcastle University.
There have been many theories of ageing, he began, including Harman’s free radical and mitochondrial theories, whereby the way we age may be linked to the way we produce free radicals. Mitochondria are a major source of reactive oxygen species (ROS) production in cells and are subject to a “vicious cycle” whereby the generation of ROS in the mitochondria create mitochondrial DNA (mtDNA) damage, which in turn damages mitochondrial function leading to the production of more ROS.
The process by which mitochondria produce adenosine triphosphate (ATP) is through the creation of a proton gradient. As this proton gradient is used to produce ATP you get a low lying leak of electrons from what is known as the respiratory chain, which consists of complexes I, II, III and IV, and different perturbations in this respiratory chain will cause an increase in the leak.
While complexes I and III are the major sites for ROS production in brain, muscle and liver tissue, Birch-Machin’s research showed that in human skin complex II is more important than previously thought, while complex III is less.
“Based on this finding we said let’s have a look at complex II in detail,” he continued, commenting on a recently published paper from May 2016, which showed that primary skin fibroblasts (although not keratinocytes) exhibited decreased mitochondrial complex II activity with age – based on an age-related decrease in both transcript expression and protein levels of complex II catalytic subunits.
Particularly interestingly, the research found that non-senescent human skin primary fibroblasts did not exhibit complex II decrease with age, and that this decrease occurred only in the senescent population of cells which have ceased to divide with age, opening some interesting paths for future study.
Birch-Machin’s talk also covered factors influencing mtDNA damage, including sun exposure where he demonstrated that the shortest wavelengths of ultraviolet radiation caused the most damage and that fibroblasts were especially sensitive. Potential interventions were discussed too; a lycopene-rich diet of tomatoes was found to increase skin protection and reduce mtDNA damage.
Box out: Smart materials
Several speakers discussed novel anti-ageing ingredients at 2016’s conference. Imke Meyer of Symrise looked at the benefits of benzylidene dimethoxydimethylindanone (BDDI), an AHR antagonist in the prevention of premature skin ageing induced by air pollution, demonstrating how Symrise’s BIO3040 ingredient reduces the diesel exhaust particle-induced expressions of melanin biosynthesis and inflammageing gene markers.
Hallstar’s Varun Mathur, meanwhile, introduced a novel mechanism to prevent solar-light induced oxidative stress. Called Micha Chemistry (after the CEO’s first grandson), the chemistry refers to a patented family of fused ring cyanoacrylates that prevent the formation of light-induced oxidative stress by stabilising photoexcited states of endogenous chromophores which can generate ROS and free radicals. This ‘fire prevention’ rather than ‘fire fighting’ approach offers some exciting possibilities when addressing the photoageing of skin.
Mathur was followed by Alain Mavon from Oriflame Cosmetics. Mavon showed delegates the methods via which Oriflame proved the lifting efficacy of its NovAge Ultimate Lift product line. The products contain a novel active ingredient for the beneficial dermal remodelling of photoaged skin: n-acetyl aspartic acid, which Oriflame found increased the expression of collagen IV and fibrillin-1 in the extracellular matrix. Tested in vivo on the forearm the ingredient increased skin firmness in 28 days, but to demonstrate this effect on facial sagging skin – where the consumer would want the product to work! – the company used air flow from a DynaSKIN device on the surface of cheek and measured the resulting 3D deformation of the skin; after 84 days of using Oriflame’s firming skin care regimen there was a notable visible reduction in the maximum depth of the air-flow induced deformation. The company also measured the height of the upper eyelid fold to ascertain the eyelid lifting properties of an n-acetyl aspartic acid-containing product, which was found to significantly decrease the height of the upper eyelid fold versus placebo.
A hairy situation
The skin on our scalp and the impact of our longer lives on our hair follicles’ health was the focus of the talk by Desmond J Tobin of the Centre for Skin Sciences at the University of Bradford. Tobin covered both thinning and greying hair, stating: “You have male pattern alopecia, the more diffuse version found in females and then there is new type of hair loss called senescent alopecia.”
This senescent alopecia, he said, is seen only in those over 60 and can be distinguished from androgenic alopecia (AGA, which begins in the late teens) or female pattern hair loss. Unlike AGA, which is caused by high levels of dihydrotestosterone (DHT), the causes of of senescent alopecia are unknown; moreover, the pattern of genes associated with senescent alopecia is completely different to that associated with male pattern baldness. Of course, individuals who are already balding can also have an overlap of senescent alopecia, Tobin added.
Ageing also heralds a change in scalp hair geometry. The structure of the hair fibre in early greying changes with the introduction of the medulla – the inner core of the hair fibre that is not present in young scalp hair, but is more common in beard hairs – and which could be an explanation for ‘wiry’ and ‘difficult’ greys.
Tobin referred to a recently published study on the importance of retaining stem cells in the hair follicle, whereby, over time, accumulating DNA damage and repeated hair cycles leads to the migration of stem cells from the follicle. Additionally, some stem cells remaining in the follicle were found to lose the key marker for functionality over time.
Tobin then asked whether we can influence how our hair ages, or reverse the damage. In answer, he highlighted several documented instances where residual stem cells were brought back to producing pigment again, and drew attention to the use of oral antioxidants to combat the effects of smoking on male pattern alopecia and hair follicle greying. He concluded by reaffirming that hair follicle ageing was, like skin ageing, linked to location, location, location with external influencers such as pollution and light impacting the way our hair follicles age, as well as internal ones.
The bigger picture
Professor Rattan’s keynote presentation came from an industry-outsider’s perspective and encouraged delegates to look at ageing from a fresh angle. “We need to know, what is this phenomenon that we are so ‘anti’?” he began, explaining that “ageing happens if you live beyond your essential lifespan… the lifespan needed by evolution to propagate the species”, which for humans is after 45 years.
“We are not programmed to age and die,” explained Rattan. “There is no ‘gerontogene’ in our body that’s trying to kill us. Evolution only works on life processes. It does its best to leave you alive to have children. But then evolution stops caring. It doesn’t try to kill you, but it does nothing to help either.”
Rattan also stressed that no two individuals age in the same way, nor do parts of the body age in the same way. And this is true even on cellular and sub-cellular levels; no two cells lose telomeres in exactly the same way, for example. “Ageing is very individualistic,” said Rattan, which means that from a prevention point of view “there will not be universal solutions”.
Life, he said, is a “biological paradox” as it is the processes which keep us alive – eating, breathing, metabolising – that age us. He acknowledged that oxygen is one of the biggest ‘enemies’ for ageing, before adding, gleefully: “Every time you breath you’re killing yourself! Basic biochemistry is full of mistakes.”
He queried the industry’s obsession with antioxidants, noting that pro-oxidative processes, such as stress-inducing exercise, fasting, mental-activity or the consumption of foods like spice and garlic are beneficial. Commenting on the theory known as ‘hormesis’, he concluded that “stress is a principle of life… a low level of stress is strengthening, but high levels will kill us.”
Day one also saw presentations from Professor Vladimir Botchkarev from the University of Bradford and Boston University, who spoke on epigenetic regulation of skin regeneration and ageing, and Marta Hlobilova, Contipro who advocated microarray as a user-friendly method of analysing gene expression, which helpfully allows for analysis of the whole transcriptome in one run and which allows for the identification or interesting (and sometimes unexpected) targets.
Day two proceedings will feature soon on www.cosmeticsbusiness.com.