Treating cutaneous aging with patented technologies.

1. Introduction Cutaneous aging is a multifactorial process affecting different constituents of the skin (Reddy and Gilchrest 2011). During aging, distribution of subcutaneous fat is altered. The subcutaneous fat is significantly lost from the dorsum of the hand, face and shin, but accumulates in the waist or thigh (Kligman et al. 1985; Farage et al. 2007). In the epidermis, signs of aging include lowering of the levels of collagen IV and collagen VII at the basement membrane, flattening of the rete ridge, thinning of the epidermis, and lowering of the levels of ceramides, free fatty acids, squalene and epidermal cholesterol (El-Domyati et al. 2002; Hayashi et al. 2003; Sandby-Moller et al. 2003; Neerken et al. 2004; Fore 2006). In the dermis, aging leads to fragmentation of elastin, an increase in collagen degradation, and a decrease in production of dermal collagen, proteoglycans and glycosaminoglycans (Giacomoni et al. 2000; El-Domyati et al. 2002; Carrino et al. 2003; Fore 2006; Varani et al. 2006; Farage et al. 2007). Owing to atrophy of the supporting dermis, the skin hydration level and skin repair capacity are reduced (Farage et al. 2009). Elderly people, therefore, are predisposed to susceptibility to skin injuries and disorders (including altered wound healing, immunologic changes, dermatologic diseases, and skin cancers). Along with the increasing understanding of the mechanism of cutaneous aging, opportunities have been brought to research into anti-aging treatment. In an earlier study, oral administration of isotretinoin was found not only to improve skin thickness, skin colour, skin elasticity and skin tone, but also to reduce pigmented lesions, mottled hyperpigmentation and wrinkles (Hernandez-Perez et al. 2000). More recently, caloric restriction has been reported to prevent or delay age-associated histomorphological changes by reducing the age-related increase in the depth of the epidermis, dermis, and fat layer, and by increasing the collagen percentage, elastic fiber fraction area and dermal fibroblast population (Bhattacharyya et al. 2005). These are only few examples of the large number of works devoted to skin rejuvenation over the past 20 years. More examples of approaches explored for treatment of aging skin are listed in table 1. These approaches can be categorized into cosmetic procedures and cosmeceutical interventions. Many of them have been evaluated clinically for skin treatment (Beer 2011; Blyumin-Karasik et al. 2011; Yokoyama et al. 2014). Apart from the advances reported in the scientific literature, innovations reported in the patent literature are also worth noticing. As these innovations may not have been documented in scientific journals due to the issue of intellectual property, patent publications are a rich knowledge source complementary to the conventional scientific literature. 2. Cosmeceuticals in the patent literature As far as the patent literature on cutaneous aging is concerned, the number of patents on cosmeceuticals much exceeds that on cosmetic procedures. This may be because cosmeceuticals in general are more convenient for self-application and are less invasive (McCullough and Kelly 2006). This gives cosmeceuticals a higher practical potential. In 2011, a patent was published on a composition comprising a dill extract, a blackberry leaf extract, and a cosmetically acceptable carrier (Kizoulis et al. 2011). In vitro studies showed that the blackberry extract stimulates tropoelastin production (Kizoulis et al. 2011). Compared to a composition containing either a dill extract or a blackberry leaf extract, the one containing

MicroRNAs as regulators of cutaneous wound healing.

MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, and have displayed important roles in areas spanning from embryonic development to skin physiology. Despite this, till now little is known about the significance of miRNAs in cutaneous wound healing. In this mini-review, we discuss the existing evidence on the roles of miRNAs in physiological processes relevant to cutaneous wound healing, followed by a highlight of the prospects and challenges of future development of miRNA-based wound therapies. With existing technologies of nucleic acid transfer and miRNA modulation, it is anticipated that once the roles of miRNAs in wound healing have been clarified, there will be a vast new vista of opportunities brought up for development of miRNAtargeted therapies for wound care.

Nucleic acid therapy for lifespan prolongation: Present and future.

Lifespan prolongation is a common desire of the human race. With advances in biotechnology, the mechanism of aging has been gradually unraveled, laying the theoretical basis of nucleic acid therapy for lifespan prolongation. Regretfully, clinically applicable interventions do not exist without the efforts of converting theory into action, and it is the latter that has been far from adequately addressed at the moment. This was demonstrated by a database search on PubMed and Web of Science, from which only seven studies published between 2000 and 2010 were found to directly touch on the development of nucleic acid therapy for anti-aging and/or longevity enhancing purposes. In light of this, the objective of this article is to overview the current understanding of the intimate association between genes and longevity, and to bring the prospect of nucleic acid therapy for lifespan prolongation to light.