Investigation into the significant role of dermal-epidermal interactions in skin ageing utilising a bioengineered skin construct.

Increased prevalence of skin ageing is a growing concern due to an ageing global population and has both sociological and psychological implications. The use of more clinically predictive in vitro methods for dermatological research is becoming commonplace due to initiatives and the cost of clinical testing. In this study, we utilise a well-defined and characterised bioengineered skin construct as a tool to investigate the cellular and molecular dynamics involved in skin ageing from a dermal perspective.

Mitigation of ultraviolet-induced erythema and inflammation by para-hydroxycinnamic acid in human skin.

Objective: To evaluate whether p-hydroxycinnamic acid (pHCA) alone and in combination with niacinamide (Nam) can mitigate UV-induced erythema, barrier disruption, and inflammation.

Methods: Three independent placebo-controlled double-blinded studies were conducted on female panellists who were pretreated on sites on their backs for 2 weeks with skin care formulations which contained 0.3% or 1% pHCA with 5% Nam, 1% pHCA alone, 1.

-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.

-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after HO and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms.

Integration of transcriptomics and spatial biology analyses reveals Galactomyces ferment filtrate promotes epidermal interconnectivity via induction of keratinocyte differentiation, proliferation and cellular bioenergetics.

Objective: Human skin is the first line of defence from environmental factors such as solar radiation and is susceptible to premature ageing, including a disruption in epidermal differentiation and homeostasis. We evaluated the impact of a Galactomyces Ferment Filtrate (GFF) on epidermal differentiation and response to oxidative stress.

Methods: We used transcriptomics, both spatial and traditional, to assess the impact of GFF on epidermal biology and homeostasis in keratinocytes (primary or immortalized) and in ex vivo skin explant tissue.

Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule.

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling.

Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models.

Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease.

The combination of allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate mitigates UVB-induced PGE synthesis by keratinocytes.

Objective: Erythema, characterized by the redness of the skin, is a common skin reaction triggered by various endogenous and exogenous factors. This response is often a result of the activation of underlying inflammatory mechanisms within the skin. The objective of this study is to investigate the potential benefits of applying a combination of skincare ingredients, namely allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate (AB5D), in the modulation of inflammatory factors associated with erythema.

Early onset of senescence and imbalanced epidermal homeostasis across the decades in photoexposed human skin: Fingerprints of inflammaging.

Inflammaging is a theory of ageing which purports that low-level chronic inflammation leads to cellular dysfunction and premature ageing of surrounding tissue. Skin is susceptible to inflammaging because it is the first line of defence from the environment, particularly solar radiation. To better understand the impact of ageing and photoexposure on epidermal biology, we performed a system biology-based analysis of photoexposed face and arm, and photoprotected buttock sites, from women between the ages of 20s to 70s.

Inspired by vitamin A for anti-ageing: Searching for plant-derived functional retinoid analogues.

Background: Cosmetic treatments that inspire one's appearance to resemble their younger portrait often utilize ingredients that confer acute effects, particularly hydration by creating hydrophobic barriers or transient elevation of barrier water content. But superior therapies successfully promote morphogenesis of the dermal-epidermal junction, inspiring extracellular matrix (ECM) formation. This can be achieved by agonism of the very well-known retinoid nuclear receptors using the endogenous ligand all- retinoic acid (tRA), tRA precursors or plant-based functional analogues, with reduced side effects.

Nicotinamide Prevents UVB- and Oxidative Stress‒Induced Photoaging in Human Primary Keratinocytes.

Nicotinamide (NAM), a NAM adenine dinucleotide precursor, is known for its benefits to skin health. Under standard culture conditions, NAM delays the differentiation and enhances the proliferation of human primary keratinocytes, leading to the maintenance of stem cells. In this study, we investigated the effects of NAM on photoaging in two-dimensional human primary keratinocyte cultures and three-dimensional organotypic epidermal models.

The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid-related bioactivity over retinol and retinyl palmitate in human skin models.

Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin.

Enhanced retinoid response by a combination of the vitamin A ester retinyl propionate with niacinamide and a flavonoid containing Ceratonia siliqua extract in retinoid responsive in vitro models.

Objectives: Retinoids have been used for decades as efficacious topical agents to treat photoaged skin. The purpose of our present research is to evaluate whether the activity of the vitamin A ester retinyl propionate (RP) can be enhanced by niacinamide (Nam) and a flavonoid containing Ceratonia siliqua (CS) fruit extract in retinoid responsive in vitro models.

Methods: Retinyl propionate was tested alone and in combination with Nam and CS in an RARα reporter cell line for promoter activation and compared to trans-retinoic acid (tRA) activation.

Metabolic dysfunction in human skin: Restoration of mitochondrial integrity and metabolic output by nicotinamide (niacinamide) in primary dermal fibroblasts from older aged donors.

Alterations in metabolism in skin are accelerated by environmental stressors such as solar radiation, leading to premature aging. The impact of aging on mitochondria is of interest given their critical role for metabolic output and the finding that environmental stressors cause lowered energy output, particularly in fibroblasts where damage accumulates. To better understand these metabolic changes with aging, we performed an in-depth profiling of the expression patterns of dermal genes in face, forearm, and buttock biopsies from females of 20-70 years of age that encode for all subunits comprising complexes I-V of the mitochondrial electron transport chain.

A population-based gene expression signature of molecular clock phase from a single epidermal sample.

Background: For circadian medicine to influence health, such as when to take a drug or undergo a procedure, a biomarker of molecular clock phase is required--one that is easily measured and generalizable across a broad population. It is not clear that any circadian biomarker yet satisfies these criteria.

Methods: We analyzed 24-h molecular rhythms in human dermis and epidermis at three distinct body sites, leveraging both longitudinal (n = 20) and population (n = 154) data.

Niacinamide mitigates SASP-related inflammation induced by environmental stressors in human epidermal keratinocytes and skin.

Objective: To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence-related biomarkers induced by environmental stressors.

Methods: Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3-D skin organotypic models were exposed to a combination of UVB and PM and treated with Nam or vehicle control.

Optimized low pH formulation of niacinamide enhances induction of autophagy marker ATG5 gene expression and protein levels in human epidermal keratinocytes.

Background: Macromolecules in skin cells are damaged when exposed to environmental stressors, leading to disrupted cellular function and homeostasis. While epidermal turnover can eliminate some of this damage, autophagy can rapidly remove these defective components. Niacinamide (Nam) is known to induce autophagy and optimizing formulations to maximize this response could provide improved homeostasis in stressed skin.

Topical niacinamide does not stimulate hair growth based on the existing body of evidence.

Niacinamide has been suggested to impact hair biology via stimulation of VEGF synthesis. Testing in an in vitro VEGF synthesis assay, it was found that niacinamide cannot stimulate VEGF synthesis across a broad dose-response range.

Nicotinamide Metabolism Modulates the Proliferation/Differentiation Balance and Senescence of Human Primary Keratinocytes.

Nicotinamide (NAM) is the main precursor of nicotinamide adenine dinucleotide (NAD), a coenzyme essential for DNA repair, glycolysis, and oxidative phosphorylation. NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3-dimensional organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation in the basal layer.

The evolving role of the NAD+/nicotinamide metabolome in skin homeostasis, cellular bioenergetics, and aging.

Human skin is exposed to daily environmental insults, particularly solar radiation, that triggers a range of molecular responses. These perturbations to the normal homeostatic state can lead to cellular dysfunction and, ultimately, impacts tissue integrity and accelerates skin aging (photoaging). One of the responses is increased oxidative stress which has been shown to disrupt cellular bioenergetics.

Nicotinamide preferentially protects glycolysis in dermal fibroblasts under oxidative stress conditions.

Background: Daily exposure of human skin to environmental insults such as solar radiation, pollution and smoke can lead to an elevation of oxidative stress, causing premature acceleration of skin ageing. Oxidative stress is known to disrupt cellular metabolism, which negatively impacts the skin's functionality at the cellular and tissue level.

Objectives: To examine the changes in cellular metabolism due to oxidative stress.

Male skin care: shaving and moisturization needs.

Historically, most cosmetic and medical cosmetic research has been focused on the female consumer. Advancements in the development of grooming instruments as well as changing consumer habits and attitudes toward male cosmetic skin care needs support the need to develop a deeper understanding of male skin biology and how that can be used to improve the quality of life relative to societal interactions. Male skin biology has been found to have unique properties that are distinct from females and have a significant impact on the way males groom and maintain their overall appearance.

Comparison of the impact of environmental stress on male and female skin.

Past research on understanding gender differences of skin biology and its response to environmental insults has focused on morphological and gross physiological comparisons. In general it has been found that male skin has a greater susceptibility to being negatively impacted by environmental stressors, in particular ultraviolet radiation. These noted differences in response to environmental insults are probably due to a combination of underlying biologically based differences and variable sun-protection and skin-care product usage between genders.

Niacinamide: A B vitamin that improves aging facial skin appearance.

Background: In multiple chronic clinical studies, topical niacinamide (vitamin B3) has been observed to be well tolerated by skin and to provide a broad array of improvements in the appearance of aging facial skin (eg, reduction in the appearance of hyperpigmentated spots and red blotchiness).

Objective: To clinically determine the effect of topical niacinamide on additional skin appearance and property end points (wrinkles, yellowing, and elasticity).

Methods: Female white subjects (N = 50) with clinical signs of facial photoaging (fine lines and wrinkles, poor texture, and hyperpigmented spots) applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks (double blind, left-right randomized).