Quantifying Wellness: Anti-aging Benefits Beyond Wrinkle Reduction

Not a day goes by without encountering articles, interviews or advertisements that contain the term well-being, which often is connected with messaging that consumers are motivated to improve their well-being with one purchase, activity, regime, etc.¹ Governments are called upon to assure the well-being of their country's population; the term well-being even figures into the World Health Organization’s (WHO’s) definition of health from 1948, although it was not further defined.² Somewhat circular is the definition of well-being found in the Random House Dictionary: a good or satisfactory condition of existence; a state characterized by health, happiness and prosperity.³

As this trend increases in strength and impact on consumer choices, the cosmetic industry cannot fall behind. In fact, wellness and the use of cosmetic products have gone hand-in-hand for decades, more or less openly claimed and promised. For example, a slogan for Guerlain's Issima Happyology cream states, "Your skin is never as radiant as when you are happy." This is a good example, except for one fact: How can you prove such a statement? Maybe it is "puffery," needing no scientific proof, but in this age of evidence-based cosmetics⁴ and even "happiness in a jar,"⁵ claims such as these require substantiation in order to have any impact.

"Hope in a Jar" was a denigrating term given to anti-aging creams and lotions suggesting more or less veiled terms to slow/stop aging or to turn back the clock on aged skin. This brings us to the first question on "anti-aging:" Do we mean to protect against too rapid aging, i.e., the preventive approach? Or do we mean to repair existing damage due to aging, i.e., the treatment approach? The last 30 years in the cosmetics industry have seen the development of literally hundreds of “active” ingredients promising some benefits in either preventive or curative mode; from vitamins to AHAs, from ceramides to liposomes, from isoflavones to antioxidants and resveratrol, from retinol to designer peptides ... during this period, the concepts, documented mechanisms and results of in vitro and/or clinical studies have also grown in complexity, sophistication and, possibly, marginal efficacy, but without truly revolutionizing the field. We may therefore ask ourselves the question: Why do consumers still buy (and use) cosmetic products?

Why Consumers Use Cosmetics

A growing number of publications discusses this question as well as consumer purchasing behavior for consumer goods described as cosmetics and/or makeup. As an aside, interestingly, for various reasons, academic studies have focused on what in the United States are called cosmetics; i.e., color cosmetics or makeup. However, the distinction of other categories of personal care, e.g., skin care, body care, hair care, etc., is not precise and many answers to the above question are equally valid for these other products and their subcategories of anti-aging, moisturizing, firming, ant-wrinkle, etc.

One blog asked:⁶ Why do they do it? That is, why do women shop for, buy and wear cosmetics? Do they buy cosmetics because they are useful or because they make [them] feel good?

The answer was: Women buy and wear makeup, they told us [the bloggers], primarily for themselves. We asked them to rank potential reasons for wearing cosmetics. Resoundingly, female respondents put, "feeling good about myself" at the top of the list.

In the same vein, research by Apaolaza-Ibañez et al. showed⁷ both the emotional and utility aspect of cosmetic brands have a significant impact on consumer satisfaction—but the emotional component has a greater effect. Some of the main positive emotions aroused by beauty products included, "the sensation of well-being gained from eliminating or reducing feelings of worry and guilt, which is the factor with the greatest impact," the author explained.⁸

In the book Hope in a Jar,⁹ historian Kathy Peiss showed how women, far from being pawns and victims, used makeup to declare their freedom, identity and sexual allure as they flocked to enter public life.

Following is a quote from the book: Today the possibilities of transformation through cosmetics is often belittled as a delusion ("hope in a jar") that only masks the fact of women's oppression. In truth, women knew then—as they do now—precisely what they were buying. […] They reported their delight in beautifying—in the sensuous creams and tiny compacts, the riot of colors, the touch of hands, ... Indeed, the pleasures of fantasy and desire were an integral part of the product…

In the Harvard Business Review of May 1, 2010, M. Silverstein and K. Sayre stated: Beauty products and services produce a sense of emotional well-being in women.¹⁰

Davan et al. studied and quantified the impact of cosmetic makeup on perceived age upon first impression,¹¹ to investigate its psychosocial and aesthetic effects. By objectively quantifying and qualifying the benefits of applying cosmetic makeup, the authors concluded it can reduce the perceived age, improve the projected first impression and increase the self-esteem of those who apply it.

While many other studies on similar topics could be cited, an excerpt from a quote in the book Just Ask a Woman, by Dan Brestle,¹² former president of Estée Lauder, says it all:

In our business there is a passion and an understanding of the business that only women can bring. The emotionalism of buying a lipstick is something lost on most marketers. It just makes you feel good. In our business, you can never discount the emotional side of the equation. … In my business, women are more knowledgeable; they understand at a deeper level how the product works; and they are passionate about their products. They love using them.

To summarize, yes, claims of anti-aging based on specific or general anti-aging active ingredients such as retinol, peptides, polyphenols, etc., are necessary and useful for marketing cosmetic products in skin care, body care and increasingly in hair care. However, they are not the major factors influencing consumer satisfaction from the products they buy. The hedonic aspects, i.e., the pleasure of using the products, the well-being afforded by them, and the psychological improvements gained from these products, are the true drivers.

In addition, the cosmetics industry recognizes with increasing awareness that claims, e.g., of complex bioactivities for DNA protection of telomerase stimulation; of -omics of all sorts; and of veiled promises for wrinkle reduction and skin repair have lost credibility and consumers’ interest. In fact, most users lack the training to understand these concepts and mechanisms.

So, what alternative message can brands then offer? Perhaps the new language in advertisements might be, "This product helps to reduce … (wrinkles, red spots, hyperpigmentation, sagging features, etc.), which will improve your self-assurance, social engagement and overall well-being by X%." The difference here being the quantitative assertion about claims that until now have never been measured and truly substantiated.

Thus, the objective of the present work was to demonstrate improved parameters for "well-being" and of (self-)perception on the basis of quantitative results afforded by a novel ingredient, and to determine if these results were coherent with the more classical approach of in vitro and instrumental clinical studies.

The hedonic aspects and pleasure of using cosmetic products, i.e., the well-being and psychological improvements gained, are the true consumer drivers.

Materials and Methods

Centcyamine¹³ (see Figure 1) is an alkaloid found in the seeds of the cornflower Centaurea cyanus. This material has been used for many years for its anti-inflammatory properties. The sample studied in the described tests was found to be a pure, perfectly characterized and safe substance.

In vitro studies: Exploratory in vitro tests were carried out with various concentrations of centcyamine using qPCR microfluidic technology^a to screen for genetic modulation in normal human dermal fibroblasts. System miniaturization has led to the development of a chip allowing for the analysis of 96 conditions vs. 96 genes. This chip integrates genes covering the entire range of skin activity, including the Klotho gene KL for skin longevity and the production of inflammatory cytokines IL-6, IL-8 as well as COX-2. Stimulation of Klotho protein synthesis was confirmed using immune-fluorescence staining and quantification by software^b.

Collagen and elastin production were compared between young and senescent cells using the same technology. Pre-senescent were defined as neoculture cells multiplied through 13 doublings until their Lamin B1 expressions diminished, indicating a pre-senescent state. The cell proliferation of normal human dermal fibroblasts (NHDF) was followed over 56 days and the cell count was compared between treated and untreated cultures.

Instrumental clinical studies: Various in vivo protocols were carried out with 60 female subjects between the ages of 45 and 65 (average age = 56). Volunteers having dry and sensitive skin and diffuse redness on the face were chosen. Thirty volunteers used a placebo formula and 30 other volunteers used a verum cream containing centyamine. The products were used twice daily. Photographic assessments were made^c and changes in redness were scored between days 1 and 56, taking into account their size, the surface and the intensity. Skin isotropy measures, characteristic of restructuring effects, were carried out^d and skin firmness was measured^e before and after 56 days of treatment. The studied parameters were surface and average depth of skin deformation.

Subjective evaluations: Each panelist was instructed to evaluate her skin first thing in the morning, in front of a mirror, every other day for 56 days, using three descriptors: homogeneity of complexion, skin radiance and skin comfort. The subjects rated each descriptor from 0 = very weak to 10 = very strong.

On day 0 of the trial, all 60 volunteers completed a self-evaluation questionnaire for quality of life/well-being, referred to as the EMMBEP (a measurement scale demonstrating psychological well-being).¹⁴ Each subject thus described, more or less, her state of well-being by answering 47 questions with scores ranging from 0 (“never”) to 5 (“almost always”), from which a global score from 0 to 100 is calculated. (Author’s comment: It must be noted that the EMMBEP questionnaire does not, in any way, refer to the cosmetic treatment, to the sensorial or hedonistic parameters of the creams).

Data was analyzed for statistical significance using the student t-test for paired data. Normality was verified using the Shapiro-Wilk method (a = 0.01). Note that clinical studies were performed during November and December, in winter months.

Results: In vitro

Klotho gene: Centcyamine increased Klotho gene expression in dermal fibroblasts. The stimulation reached 244% relative to the control (see Figure 2). This activation of Klotho gene expression also was confirmed at the protein level, where centcyamine increased the synthesis of Klotho by 44% relative to the control. As expected for a secreted and membrane localized protein, Klotho was observed around the nuclei in the endoplasmic reticulum.

NHDF: The proliferation of NHDF was slightly reduced by centcyamine treatment (data not shown), although no morphological difference was observed between treated and untreated fibroblasts and there was no apparent cytotoxicity.

Derma matrix: In untreated, pre-senescent fibroblasts, collagen I and elastin synthesis rates were reduced by 16% and 22%, respectively, compared with young cells. However, in pre-senescent NHDF cells treated with centcyamine, the expression of both proteins was maintained at the level found in young cells (see Figure 3). Thus, treatment with centcyamine preserved the cells from age-induced decreases in collagen I and elastin synthesis (see Figure 4).

Soothing activity: Skin exposure to external stress may lead to the expression of inflammation mediators and subsequent irritation. Inflammation can propagate and affect dermal cells, resulting in chronic inflammation or inflammaging.¹⁵ The expression of COX-2 also increases with age and contributes to skin aging. Taking basal cytokine and prostaglandin gene expression as 100% in untreated cells, however, centcyamine at a concentration of 3 ppm reduced the expression of IL-6, IL-8 and COX-2 in dermal fibroblasts by 55%, 56% and 64%, respectively (see Table 1).

This result is in line with the known anti-inflammatory effect of cornflower preparations. Indeed, for many years, cornflower infusions have been prescribed in case of eye and eyelid irritation and to fight against conjunctivitis and inflammation of the skin.

In summary, in vitro, this active molecule, first identified in cornflower extracts by Sarker et al.,¹⁶ was found to increase Klotho protein synthesis. The Klotho protein slows cell proliferation rates and thereby ensures cell homeostasis. It also regulates various growth signals, limiting lamin B1 expression on one hand (data not shown) and supporting dermal matrix protein synthesis (collagen I and elastin) on the other hand, even in senescent cells. These pathways result in the protection and extension of cell viability. Moreover, centcyamine inhibited inflammation mediators involved in the aging process. It is for these protective effects against symptoms of aging that scientists have referred to Klotho as the "youth hormone."¹⁷

Women under high chronic stress had lower levels of Klotho. These decreases were age-dependant and related to states of well-being.

Results: Clinical Studies

In spite of climatic influences (i.e., winter weather conditions), which degraded skin firmness in the placebo group, a significant difference (p < 0.006) was observed in the evolution of this parameter between the two groups, where skin elasticity was maintained in the treated group (see Figure 5).

The skin firmness data^d also show improved skin isotropy in the centcyamine-treated panelists, but a degradation of this feature in the placebo group (p = 0.057; data not shown).

Photographs^c demonstrated improved homogeneity of skin tone over the period of the study as the red blotches were notably and significantly reduced in the treated group, in contrast to the placebo panel (see Figure 6).

However, most importantly, these instrumental results were reflected in panelist’s scores of self-perception, with a clear but unconscious advantage for the verum cream over the placebo cream (see Figure 7). Shown here are the averages of the 30 scores taken every other day by the volunteers in the two groups. The consumers clearly were able to see the benefits of using the test cream. A statistical difference between the two groups (p < 0.05) was achieved around day 34 although over time, the differences decreased for reasons not further explored at this time. Explanations may include climate, holiday season stress, etc.

Finally, the well-being questionnaire EMMBEP showed improvements in parameters of self-esteem, happiness, sociability and overall scores. The volunteers using the verum cream, in contrast to those using the placebo, estimated being happier (+50), more peaceful (+60), more committed (+80) and more stable in the society (+20), with an improved global wellness (+30). These results were particularly noticeable in the group of volunteers who saw the best results in redness reduction (40% of the panel). The authors therefore confirmed an interesting correlation between well-being scores, instrumental observations and self-assessment and, indirectly, with in vitro mechanistic data (see Table 2 and Figure 8).

Discussion and Conclusions

This study presents in vitro data showing a novel ingredient, centcyamine, possesses properties that help to explain clinical data observations; i.e., decreases in inflammatory markers, a delay in the onset of senescence and increases in the gene expression and synthesis of the Klotho protein.

Instrumental measurements on 60 panelists further demonstrated stronger resilience in centcyamine-treated skin (30 panelists) against external aggressors, including the maintenance of skin elasticity, an improved skin roughness profile and a reduction in redness and irritation.

Moreover, panelists could observe detailed results by the subjective evaluation of their faces in a coherent and continuous way. For the first time, such a study was accompanied by the use of a validated well-being questionnaire, which was completed before and after the trial period. Changes indicated improved well-being scores aligned with improved facial features.

However, as the old statistics adage goes, "Correlation does not indicate causation,"¹⁸ and this study is not suggesting the centcyamine substance itself induces well-being sentiments in the brain, even if it is known that increased levels of circulating Klotho protein are correlated with lower stress symptoms. A recent study provided first evidence of this; specifically that the amount of detected Klotho in one’s circulation is sensitive to environmental influences, especially to chronic psychosocial stressors. This data revealed women under high chronic stress had significantly lower levels of Klotho, in comparison with low-stress controls; interestingly, the rates of decrease were age-dependent and related to states of well-being.¹⁹

While the pleasure (hedonic) aspects of using a cosmetic product can be measured on the spot and focus on immediate sensations, e.g., sensory experiences, the long-term psychological benefits of quality cosmetic formulations require different approaches. The results of the present work suggest a new path to cosmetic research and marketing. The novel sensorial, perceptional and neuroscientific methods used to demonstrate consumer-perceivable cosmetic benefits are more subjective and psychological and can thus be based on specifically targeted ingredients and original pertinent measurement methods.

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