An updated review of clinical methods in the assessment of ageing skin – New perspectives and evaluation for claims support

With the advancement of skin research, today's consumer has increased access to an informed understanding of ageing skin and its appendages, together with a plethora of targeted products to meet such needs. In recent years, increased legislative demands for quality evidential claims support have led not only to the development and validation of clinical methods to measure and quantify ageing skin, but also a clearer understanding of the skin ageing process–especially the impact of both its internal and external environments–as well as a tougher stance on clearly unjustifiable claims. Traditional testing methods used to research and evaluate anti‐ageing products claim to employ sophisticated instruments. Today, however, since the term anti‐ageing can be considered a misnomer, intelligent use of combined more advanced clinical methods has enabled the development of technologically improved consumer products providing enhanced efficacy and targeted performance. Non‐invasive methods for the assessment and quantification of the causes of ageing skin provide tools to the clinical researcher as defined by key clinically observed ageing parameters. Where evidence requires additional support, a number of clinical procedures evaluating ageing skin and hair products are combined with invasive procedures, thus enabling an added value to product claims. As discussed herein, given the enhanced understanding of ageing, we provide an update to our previous reviews of clinical methods used in the assessment of skin ageing, to include the wider aspects of environmental exposure; skin pigmentation; microbiome disturbance; surface topography; colour, radiance, and pH; and structural integrity–all requiring a disciplined approach to their use in dermatological investigations and product claims evidence.     

A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part I: Cellular and molecular perspectives of skin ageing

The ageing process is noticeable within all organs of the body and manifests itself visibly in the skin. Skin ageing is influenced by several factors including genetics, environmental exposure, hormonal changes and metabolic processes. Together these factors lead to cumulative alterations of skin structure, function and appearance. The functioning of the central nervous, immune, endocrine and cardiovascular systems, as well as the skin is also impaired with age. Chronologically, aged skin is thin, relatively flattened, dry and unblemished, with some loss of elasticity and age-related loss of architectural regularity. General atrophy of the extracellular matrix is reflected by a decrease in the number of fibroblasts. Reduced levels of collagen and elastin, with impaired organization are primarily because of decreased protein synthesis affecting types I and III collagen in the dermis, with an increased breakdown of extracellular matrix proteins. Oxidative stress is considered of primary importance in driving the ageing process. The original free radical theory of ageing purported that the molecular basis of ageing was derived from a lifetime accumulation of oxidative damage to cells resulting from excess reactive oxygen species (ROS) produced as a consequence of aerobic metabolism. Although the skin possesses extremely efficient anti-oxidant activities, during ageing, ROS levels rise and anti-oxidant activities decline. The ROS are necessary in multiple MAP kinase pathways and the induction of AP-1, in turn, up-regulates expression of matrix-metalloproteinases providing a plausible mechanism for the increased collagen degradation in aged human skin.     

Intrinsic and extrinsic factors in skin ageing: a review

As the proportion of the ageing population in industrialized countries continues to increase, the dermatological concerns of the aged grow in medical importance. Intrinsic structural changes occur as a natural consequence of ageing and are genetically determined. The rate of ageing is significantly different among different populations, as well as among different anatomical sites even within a single individual. The intrinsic rate of skin ageing in any individual can also be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. Photodamage, which considerably accelerates the visible ageing of skin, also greatly increases the risk of cutaneous neoplasms. As the population ages, dermatological focus must shift from ameliorating the cosmetic consequences of skin ageing to decreasing the genuine morbidity associated with problems of the ageing skin. A better understanding of both the intrinsic and extrinsic influences on the ageing of the skin, as well as distinguishing the retractable aspects of cutaneous ageing (primarily hormonal and lifestyle influences) from the irretractable (primarily intrinsic ageing), is crucial to this endeavour.     

Relationship between clinical features of facial dry skin and biophysical parameters in Asians

There have been few reports classifying the biophysical characteristics of Korean women with healthy skin. Consequently, the aim of this study was to find the most useful parameters for categorizing skin types based on a clinical assessment. One hundred and three female volunteers, aged 20-59, participated in this study. We conducted a self-evaluation questionnaire, a clinical assessment of the facial skin, and non-invasive measurements on the cheek under controlled environmental conditions. The questionnaire survey indicated that 72% of respondents had dry skin. However, results of the clinical assessment focusing on skin roughness and scaling of the cheek showed that 6 subjects had very dry skin (6%), 29 had dry skin (28%) and 68 had normal skin with sufficient moisture (66%). We analysed the correlation between the clinical assessment and biophysical parameters. As a result, we obtained six biophysical parameters that had relatively higher correlations with clinical assessment than other parameters. Our study provided general information about the physiological characteristics of normal skin in Korean women and suggested useful parameters for characterizing dry skin.     

In vivo confocal fluorescence imaging of skin surface cellular morphology: a pilot study of its potential as a clinical tool in skin research

The cellular morphology of the stratum corneum was studied in vivo using a novel imaging technique that uses confocal fluorescence microscopy in combination with topical application of a fluorescent contrast agent. Images obtained with this method show a strong variation in skin surface cellular morphology among healthy subjects. The results of several clinical studies suggest that cellular morphology is affected by the efficiency of the process of desquamation. As such, cellular morphology shows strong potential to serve as an indicator of skin health that yields mechanistic insight into the origins of skin ailments, such as xerosis, and the effectiveness of their treatments.     

The regulatory role of the tetrapeptide AcSDKP in skin and hair physiology and the prevention of ageing effects in these tissues – a potential cosmetic role

The naturally occurring tetrapeptide acetyl‐N‐Ser‐Asp‐Lys‐Pro (AcSDKP) recognized as a potent angiogenic factor was shown recently to contribute to the repair of cutaneous injuries. In the current article, we report the ability of AcSDKP to exert a beneficial effect on normal healthy skin and scalp and to compensate for the ageing process. In vitro AcSDKP at 10^?11–10^?7 M significantly stimulates the growth of human keratinocytes, fibroblasts and follicle dermal papilla cells. Moreover, it enhances the growth of human epidermal keratinocyte progenitor and stem cells as shown in a clonogenic survival assay. Topical treatment of ex vivo cultured skin explants with 10^?5 M AcSDKP increases the thickness of the epidermis and upregulates the synthesis of keratins 14 and 19, fibronectin, collagen III and IV as well as the glycoaminoglycans (GAGs). In the ex vivo‐cultured hair follicles, AcSDKP promotes hair shaft elongation and induces morphological and molecular modifications matching the criteria of hair growth. Furthermore, AcSDKP at 10^?11–10^?7 M was shown to improve epidermal barrier, stimulating expression of three protein components of tight junctions (claudin‐1, occludin, ZO‐1) playing an important role in connecting neighbouring cells. This tetrapeptide exercises also activation of SIRT1 implicated in the control of cell longevity. Indeed, a two‐fold increase in the synthesis of SIRT1 by cultured keratinocytes was observed in the presence of 10^?11–10^?7 M AcSDKP. In conclusion, these findings provide convincing evidence of the regulatory role of AcSDKP in skin and hair physiology and suggest a cosmetic use of this natural tetrapeptide to prevent skin ageing and hair loss and to promote the cutaneous regeneration and hair growth.     

Oxidative stress and cutaneous ageing: the 'toxic second messengers' concept and an interesting family of products, 'pseudodipeptides'

There are a number of factors responsible for cutaneous ageing. Apart from genetically programmed cell ageing, different external aggressors, such as solar radiation, pollution and stress, can accelerate this phenomenon. It is now accepted that deleterious oxidations of live mediums are of major importance. This so-called 'oxidative stress' is a very complex situation that covers a large number of chemical reactions, and involves very diverse oxidizing species. Being aware of this complexity, and aiming to obtain a 'universal protection' against oxidative stress, we have tailored specific protective agents. At the same time, it was necessary to design new experimental models for the evaluation of antioxidants' efficiency. Our studies have revealed that cutaneous tissue also needs protection against non-radicalar, toxic-oxidizing molecules, which we called 'toxic second messengers' of oxidative stress [1]. These molecules, against which live mediums have very poor self-defence mechanisms, are key intermediates in the oxidative reactions. They are responsible for irreversible damage, such as the deactivation of enzymatic complexes and loss of the skin's elasticity, or even DNA damage. This better understanding of oxidative stress mechanisms of action allowed us to design original protective agents against toxic second messengers, called 'pseudodipeptides'. In order to obtain a topically active compound, we have synthesized several 'biomimetic and biocompatible molecules' with improved activities and a longer life on the skin. It was also necessary to design specific tests in order to prove the unique properties of pseudodipeptides. Several experiments have been carried out, with the aim being to be as close as possible to conditions in vivo and more particularly to demonstrate their 'lipid peroxidase-like' activity or their efficiency against 'toxic aldehydes': HNE, from the oxidation of phospholipids [1], and glucosone, from that of sugars. More recent experimental designs have revealed the involvement of transition metals in oxidative stress and demonstrated that pseudodipeptides can 'detoxify' transition metals without interfering with useful biological mechanisms that also use transition metals. Finally, the anti-aging efficiency of pseudodipeptides was proven ex vivo and allowed us to present them as biocompatible and biomimetic compounds with a real polyvalent protective and repairing anti-oxidative activity.     

A combined approach in characterization of an effective w/o hand cream: the influence of emollient on textural, sensorial and in vivo skin performance

To formulate a consumer-acceptable cosmetic product, numerous demands have to be fulfilled, and as the most important, efficacy (both real and perceived), adequate aesthetic (visual perception) and all sensorial characteristics have to be achieved. In this study, four model water-in-oil creams intended for hand care, varying in one emollient component, were submitted to rheological, sensory and textural characterization, and their efficacy was evaluated in in vivo study on human volunteers. Our results indicate that certain alteration restricted to the oil phase induced a change in all investigated characteristics, showing that each instrumental measurement can be used as a sensitive tool in the characterization of cream samples. Regarding the correlation between physical measurements and certain sensory attributes, it is possible to formulate a product with specific sensory characteristics by using pre-defined rheological or textural parameters. To obtain a complete sensory profile of a cosmetic product, a detailed sensory evaluation should be carried out according to the existing standard practices, which are both time- and money-consuming. However, a modified sensory study could be useful for fast in-line screening along with instrumental characterization of a novel cosmetic emulsion product and could be particularly helpful in the process of distinguishing a single formulation from several differing in one component.