Hormesis-Based Anti-Aging Products: A Case Study of a Novel Cosmetic

Abstract

ᮀ Application of hormesis in aging research and interventions is becoming increasingly attractive and successful. The reason for this is the realization that mild stress-induced activation of one or more stress response (SR) pathways, and its consequent stimulation of repair mechanisms, is effective in reducing the age-related accumulation of molecular damage. For example, repeated heat stress-induced synthesis of heat shock proteins has been shown to have a variety of anti-aging effects on growth and other cellular and biochemical characteristics of normal human skin fibroblasts, keratinocytes and endothelial cells undergoing aging in vitro. Therefore, searching for potential hormetins -conditions and compounds eliciting SR-mediated hormesis -is drawing attention of not only the researchers but also the industry involved in developing healthcare products, including nutriceuticals, functional foods and cosmeceuticals. Here we present the example of a skin care cosmetic as one of the first successful product developments incorporating the ideas of hormesis. This was based on the studies to analyse the molecular effects of active ingredients extracted from the roots of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of mRNAs and proteins in human skin cells. The results showed that the ginsenosides extracted from Sanchi induced the transcription of stress genes and increased the synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70, in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract also has significant positive effects against facial wrinkles and other symptoms of facial skin aging as tested clinically, which may be due to its hormetic mode of action by stressinduced synthesis of chaperones involved in protein repair and removal of abnormal proteins. Acceptance of such a hormesis-based product by the wider public could be instrumental in the social recognition of the concept of hormesis as the beneficial effects of mild stress of choice, and will encourage the development of novel health care products with physical, nutritional and mental hormetins.

Variation in Hsp70-1A Expression Contributes to Skin Color Diversity

“…These dual roles of Hsp70-1A in determining pigmentation both in melanocytes and in keratinocytes were considered to be clearly reflected in Hsp70 inhibitor-driven skin lightening and Hsp70-1A activator-driven skin darkening in ex vivo skin tissues. In addition, it has been reported that overexpression of Hsp70-1A inhibited UV-induced epidermal hyperplasia, degradation of extracellular matrix, and decreased skin elasticity that would characterize skin photoaging in SKH-1 mice (Matsuda et al, 2013), which led several cosmetic and/or skin care companies to launch products that counteract UV-induced premature skin aging via the activation and/or increased expression of Hsp70-1A (Rattan et al, 2013). Taken together, Hsp70-1A would be an essential player in skin protection against UV exposure, not only through its known efficacy in repairing cellular damage but also its previously unreported roles in regulating multiple stages of pigmentation.…”

Hormetins as Novel Components of Cosmeceuticals and Aging Interventions

“…Hormetins can strengthen the homeodynamics, increase robustness of the system and enhance resilience [29]. Just as in the case of exercise-induced hormetic benefits via heat shock protein synthesis, hormetins such as ginsenosides in the cosmeceutical formulations [48] may be considered as performing a kind of intracellular molecular exercise. Certain CR mimetics may prove to be effective hormetins acting via autophagic and sirtuin-dependent SR pathways [49][50][51][52][53].…”

“…An example of a successful skin care cosmetic product developed by incorporating the ideas of hormesis is based on the studies to analyse the molecular effects of active ingredients extracted from the roots of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of mRNAs and proteins in human skin cells [48] The results showed that the ginsenosides extracted from Sanchi induced the transcription of stress genes and increased the synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70, in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract also has significant positive effects against facial wrinkles and other symptoms of facial skin aging as tested clinically, which may be due to its hormetic mode of action by stress-induced synthesis of chaperones involved in protein repair and removal of abnormal proteins [48]. (also see: http://www.givenchybeauty.com/en/skincare/vaxin-for-youth/inspiration).…”

Molecular Gerontology: From Homeodynamics to Hormesis

“…Instead, they initially cause molecular damage by virtue of their electrochemical properties and have a typical biphasic hormetic dose response. Some examples of nutritional hormetins involving heat shock response (HSR) are phenolic acids, polyphenols, flavonoids, ferulic acid, geranylgeranyl, rosmarinic acid, kinetin, zinc, and the extracts of tea, dark chocolate, saffron and spinach [42]".…”

“…Discovering novel hormetins by putting potential candidates through a screening process for their ability to induce one or more SR pathways in cells and organisms can be a promising strategy [42]. Recently, a general scheme for screening natural and synthetic single compounds or complex extracts for potentially hormetic use for human beings has been put forward [30].…”