The anti-ageing category is a rising star with the global anti-ageing products market size projected to grow to US$17.2bn from 2019-23[1].
Demographics are shifting towards a more mature population and the growing number of 30-45-year-olds are fuelling this market’s growth. The importance of a ‘healthy’ appearance and the desire to look young are among the key drivers for this expansion. Consumers are looking for products that help them make the most of their appearance, maintain skin health and prevent signs of early ageing.
Intrinsic ageing, also called chronoageing, is the result of inevitable changes occurring naturally within the body and is genetically determined. Recent research has demonstrated that skin exposure to external factors is key to the early onset of ageing processes.
Extrinsically, sun exposure induces photoageing, defined as the damage resulting from chronic UV exposure, while a chronic inflammation process triggers so-called inflammageing. These all cause the decay of skin structure.
State-of-the-art epigenetics
Every individual is unique according to their DNA composition. But the same genetic heritage does not necessarily result in the exact same physical appearance, as we can see from the way identical twins age. This is due to epigenetic science, defined as the modulation of gene-to-protein expression through the activation or deactivation of genes’ expression or translation without altering the DNA itself.
Lifestyle, environment and emotions are far more important than the genetic programme of an individual, as they can trigger processes leading to the acceleration of ageing. Increasing scientific data highlight the contribution of epigenetic mechanisms (for instance histone modification, DNA methylation and non-coding RNA production) in organs and skin ageing processes.
Figure 1:
nc886 expression decrease demonstrated with in situ hybridisation on skin explants
Among these epigenetic regulations, non-coding RNA (ncRNA) have important settlement roles in proper body functioning and in a variety of pathological conditions. They are a prime target of the pharmaceutical industry, as they have been found to function in various biological processes, such as cell proliferation, differentiation and the regulation of gene expression.
This ncRNA family can be categorised into two groups according to their length: small non-coding RNA (as micro RNA and small interfering RNA – below 30 nucleotides) and long non-coding RNA (more than 100 nucleotides). Recent studies have investigated the role of non-coding RNA in the skin, focusing on the task of protecting it against damages caused by UV light or stress.
Exploring new epigenetic pathways and allowing a better understanding of the influence of external factors on gene expression will provide new ways to tackle and delay the appearance of unwanted signs of ageing.
A new target: RNA nc886
A newly explored target called long non-coding RNA 886 (nc886) was recently recognised as a key regulator of PKR, a protein known to increase during age-related neurological diseases and associated with increased inflammation levels; nc886, due to its structure, was found to physically interact with PKR to deactivate it.
For the first time in cosmetics the impact of nc886’s activities in the skin and its contribution to ageing were investigated.
Here, Clariant Active Ingredients and its South Korean partner BioSpectrum present research on the newly-discovered correlation between ageing and the decrease of nc886 expression.
On skin explants from 19-74 years old (in situ hybridisation method); a drastic decrease of nc886 from 40 years of age onwards has been demonstrated. UVB exposure also strongly inhibits the expression of nc886.
Through extensive research, nc886 was identified as a root cause of all types of ageing: chronoageing, photoageing and inflammageing. Targeting this long non-coding RNA goes to the heart of real causes of ageing processes.
Figure 2:
nc886 synthesis increase under basal condition and UVB stress
Control of ECM-related markers
A consequence of nc886 decrease with age is stimulation of the production of MMP-9, a metalloproteinase that degrades collagen type IV, one of the major components that maintains dermal-epidermal junction (DEJ) structure and integrity.
As a result, skin structure and resilience are impaired. Skin will lose its elasticity and allow visible signs of ageing to appear. Therefore, proper expression of nc886 is necessary.
Epseama, a new active ingredient that boosts nc886 synthesis, was shown to inhibit MMP-9 expression. Consequently, collagen IV degradation is prevented and its presence is substantially improved.
In addition, by inducing the production of collagens VII and XVII, as well as the production of laminin 5, the ultrastructure of the DEJ is strengthened. As a result, communication between the dermis and epidermis is improved, and the fundamental role of the DEJ is recovered.
Epseama also heightens keratinocytes proliferation by improving the synthesis of CD44 hyaluronic acid receptors, a marker of skin homeostasis involved in the transmission of cell signals. This enhances epidermis thickness.
The new ingredient helps to preserve the integrity of ECM components and the DEJ, thus contributing to skin self-renewal and strengthening the skin’s self-defense ability.
Figure 3:
Inhibition of MMP-9 and collagen IV degradation prevention
The inflammasome pathway
Inflammation processes are important players in ageing, more particularly in inflammageing: the result of chronic inflammation accumulation. One essential protein platform involved in inflammation mediation is the inflammasome NLRP3.
This inflammasome platform is known to be activated by PKR as it is a key contributor to inflammation and inflammation mediation. We demonstrated that NLRP3 is increased in aged skin, and its downstream activities (maturation of pro-caspase 1 into caspase 1, which then induces IL-1b and IL-18 secretion) increase in aged skin as well. This supports the crucial role of inflammation in skin ageing.
Experimental data indicates the ingredient’s ability to significantly protect the epidermis after UV-radiation, and on top of that inhibit the inflammasome pathway activation that goes along with photoageing.
Long non-coding RNA 886 was recently recognised as a key regulator of PKR, a protein associated with increased inflammation levels
A sea superfood
Consumers are now concerned with the origin of the ingredients entering their cosmetic products. Authentic, environmentally friendly, natural and ethical products are sparking their interest. Moreover, seaweed is growing in popularity due to its high mineral content and rich antioxidant levels.
Derived from a ‘superfood of the sea’, Epseama draws on the nutrient power of the brown seaweed Laminaria japonica for its efficacy. It is one of the most commonly cultivated and consumed algae in Asia and is farmed off the coast of a South Korean island through responsible aquaculture practices.
Proven rejuvenation
Clariant Active Ingredients looked in-depth at the first holistic skin rejuvenator influencing a long non-coding RNA and demonstrated its success in increasing the production of nc886, leading to results such as improved skin moisture, deletion of age-related spots and a decrease in various wrinkle types including nasolabial wrinkles.
Epseama’s performance was confirmed in clinical trials on 19 women over 50 years old after only four weeks. Difficult to remove nasolabial wrinkles are smoothed: reduced by 19% in volume and 10% in roughness. Spots are decreased by 10% and skin moisture levels are increased by 14%.
Epseama draws on the nutrient power of the brown seaweed Laminaria japonica for its efficacy
Market opportunities
By 2050, the over-60s are projected to make up over 21% of the global population[2]. This presents a big opportunity for the personal care industry. Understanding the biological processes that influence skin ageing mechanisms gives us a unique focus to develop advanced innovative ingredients to delay it.
Ideally, this should be supported by a natural focus and good traceability, which fit with consumer preferences.
By uniquely targeting nc886, Epseama offers formulators a new source of rejuvenation, erasing age-related and photo-related signs, tackling the true causes of skin ageing with an ingredient derived from the sea.
Author
Julie Droux, Clariant Active Ingredients
www.clariant.com/active-ingredients
References
1. Global Anti-Aging Products Market 2019–2023, Technavio. https://bit.ly/2GTvOC5
2. World population projected to reach 9.8 billion in 2050, and 11.2 billion in 2100. https://www.un.org/development/desa/en/news/population/world-population-prospects-2017.html
