The research team also confirmed that the novel blend offered a comprehensive, four-pronged approach to anti-ageing by simultaneously addressing oxidative stress, glycation damage, declining cellular renewal, and the disruption of the skin’s internal clock.
To the researchers’ knowledge, this was “one of the first reports showing a cosmetic ingredient that significantly increases melatonin levels in ex vivo human skin”.
The study’s findings could advance the understanding of efficacy testing methods for these properties, which is a major boost for cosmeceutical development.
Addressing the four pillars of skin ageing
The research team set out to investigate the novel blend’s ability to combat the key interconnected factors that cause skin to age — oxidative stress, glycation, impaired autophagy (cellular clean-up), and circadian rhythm disruptions.
Ageing skin is constantly bombarded by free radicals, particularly from UV radiation, which causes oxidative stress. This stress damages key cellular components like DNA and proteins.
At the same time, this damage is made worse by the process of glycation, where sugars react with proteins to form harmful compounds called advanced glycation end-products (AGEs). These AGEs cause the stiffening and yellowing of collagen and elastin, leading to wrinkles and loss of elasticity.
Adding to the problem is the age-related decline of autophagy, the essential cellular cleaning process that degrades and recycles damaged components. Finally, disruptions to the skin’s circadian rhythm, or internal 24-hour clock, compromise its natural repair cycles.
These pathways are intricately linked. Oxidative stress accelerates AGE formation, which in turn impairs autophagy. The circadian rhythm, regulated by molecules like melatonin, plays a crucial role in coordinating all these repair and metabolic functions.
Significant results against environmental damage
Using a series of laboratory and human skin models, the researchers demonstrated the blend’s potent protective and restorative capabilities.
In fibroblast cells exposed to simulated UVA radiation, the blend showed powerful antioxidant effects. It significantly reduced markers of DNA damage by over 41%. It also decreased damaging reactive oxygen species (ROS) by 25.35% and mitochondrial ROS by 60.37%.
Crucially, the blend boosted the cell’s natural defences, increasing the activity of the key antioxidant enzyme superoxide dismutase (SOD) by 143.52%, and cellular energy (ATP) levels by 79.2%.
Further testing on a full-thickness skin model, designed to mimic environmental stress, showed dramatic improvements in tissue health. The blend reduced the content of damaging carbonylated products (a measure of protein oxidation) by 82.49%.
The treatment also increased the live cell layer thickness of the epidermis by nearly 390% and boosted the number of vital fibroblasts in the dermis by over 48%.
The anti-oxidative efficacy is clear across multiple cellular components. It was found to shield the cell’s power plants, protect its DNA, and preserve the essential structure of the skin against external aggressors.
Protection and renewal
The blend also proved highly effective at tackling the protein-stiffening effects of glycation. In ex vivo human skin tissue subjected to stress, the blend’s concentration was found to reduce levels of the harmful AGE, Nε-carboxymethyllysine (CML), by more than 31%.
The dual-stressor model used in the study simulated real-world environmental and metabolic skin stressors, which made this anti-glycation result highly relevant to in vivo conditions.
Beyond protection, the ingredient actively enhanced the skin’s ability to renew itself. It was found that in fibroblast models, the blend significantly promoted the process of autophagy. LC3a and LC3b — crucial markers for the formation of autophagosomes (structures that carry waste) — increased by 97%. The total number of autophagic vesicles also saw a 27% increase.
These results indicate that by promoting cellular clearance of damaged proteins and organelles, the blend could restore proteostasis and significantly contribute to anti-ageing efficacy through improved autophagic function.
The melatonin breakthrough
The study’s most pioneering finding related to the blend’s influence on the skin’s internal clock. The blend, which used advanced plant small RNA (PSR) technology to combine properties of the lavender extract and the peptide, significantly enhanced factors related to circadian rhythm regulation.
In skin cells, the content of nocturnin, a circadian rhythm control gene, increased by 23%.
Notably, in ex vivo human skin tissue treated topically with the blend for seven consecutive days, melatonin production increased by 10.69%. Melatonin is integral to regulating circadian rhythms and promoting vital night-time repair. With age, peripheral melatonin synthesis diminishes.
The findings revealed that topical application of the blend enhanced endogenous cutaneous melatonin production, marking the first reported instance of a cosmetic ingredient significantly boosting melatonin synthesis in ex vivo human skin.
Furthermore, this integrated action translated into significant structural benefits. The ex vivo skin models showed a dramatic enhancement of extracellular matrix (ECM) components following treatment.
Collagen fibres, the main structural component of the skin, improved by 61.54%, while Type I collagen soared by 280.95%. Elastic fibres and water-retaining glycosaminoglycans also saw improvements of 15.63% and 682.35%, respectively.
These profound effects on skin structure and function affirm the blend’s comprehensive anti-ageing benefits, mitigating ECM loss, which is a hallmark of dermal ageing.
Next steps
While the current research provides robust mechanistic insights using advanced skin models, the researchers acknowledged that in vivo clinical studies are the next essential step to validate the long-term efficacy, safety, and real-world applicability of the blend in diverse populations and skin types.
They wrote in conclusion: “The blend addresses skin ageing by offering multifaceted benefits — antioxidant, anti-glycation, autophagy enhancement, and melatonin production, marking a pioneering contribution to cosmetic ingredients that significantly boost melatonin production.
“Our findings advance the understanding of in vitro and ex vivo efficacy testing methods for these properties, aiding cosmeceutical development.”
Source: International Journal of Cosmetic Science
“A Lavandula angustifolia flower extract and dipeptide-4 blend modulates oxidative, glycative, autophagic and circadian pathways in human skin models”
https://doi.org/10.1111/ics.70041
Authors: Lina Wang, et al.
